PTCH1c.3141T>GBenign

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Variant interpretation report

PTCH1 c.3141T>G, p.(Leu1047=)

NM_000264.5:c.3141T>G NP_000255.2:p.(Leu1047=) View identifiers

Classification

Benign

Variant description:

No variant summary was recorded for this case.

Five-step scale from benign to pathogenic. This variant is benign. Select a step to read what it means.

Benign.A benign classification under the recorded framework.

In plain language

Gene-level background from the recorded interpretation.

About PTCH1

No gene-level summary was recorded for this case.

Key facts

Evidence used: 1 stand alone (benign) · 2 strong (benign) · 3 supporting (benign)
Expert rules: Not recorded
Other laboratories (ClinVar): 11 Benign · 1 benign
Pipeline record: 23 Jun 2026

Evidence considered

View criteria

Applied evidence criteria

BA1 (stand alone): The variant is present in gnomAD v2.1 at an allele frequency of 2.33% (grpmax filtering AF=10.84% in the African/African American population), far exceeding the BA1 threshold of >1%. A total of 307 homozygotes are observed in gnomAD v2.1. In gnomAD v4.1, AF=1.22% with 872 homozygotes. For an autosomal dominant disorder (Gorlin syndrome) with high penetrance, this frequency is incompatible with pathogenicity.
BS1 (strong): The variant allele frequency of 2.33% in gnomAD v2.1 exceeds the BS1 threshold of >0.3% for a dominantly inherited disorder. This frequency alone is sufficient strong evidence for a benign classification, though it is subsumed by the stand-alone BA1 criterion.
BS2 (strong): The variant is observed in the homozygous state in 307 individuals in gnomAD v2.1 and 872 in gnomAD v4.1. For PTCH1, which causes Gorlin syndrome (an autosomal dominant disorder with high penetrance and significant morbidity), observation of homozygosity in healthy population databases is incompatible with pathogenicity. A homozygous pathogenic PTCH1 variant would be expected to be lethal or cause severe disease.
BP4 (supporting): SpliceAI predicts no significant splicing impact (max delta score = 0.06, well below the clinically significant threshold of 0.1). Multiple in silico splicing prediction tools cited in the ClinVar submission concur that the variant does not affect normal splicing. This supports a benign interpretation for this synonymous variant.
BP6 (supporting): This variant is classified as Benign in ClinVar by 12 clinical diagnostic laboratories (Variation ID 255681), with criteria provided. Multiple submitters independently reached a benign classification, consistent with a reputable source classification for BP6.
BP7 (supporting): NM_000264.5:c.3141T>G is a synonymous variant (p.Leu1047=). SpliceAI predicts no splicing impact (max delta = 0.06, well below 0.1 threshold). The high population frequency (AF=2.33%) is inconsistent with evolutionary conservation at this position. These findings satisfy BP7 criteria for a synonymous variant with no predicted impact on splicing or protein function.

LYFE Sciences is an AI system, and it can make mistakes. Criteria may be applied incorrectly, sources may be misread, and a confident-looking classification can still be wrong. Double-check every criterion and its underlying evidence before relying on any call.

01The reasoning

How it was classified

The recorded framework is Not recorded. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.

Recorded applied criteria

The applied criteria and their strengths are shown as assessed under the stated framework.

Pathogenic evidence criteria: 0 Benign evidence criteria: 6

Pathogenic criteria applied · 0

No pathogenic criterion marked as applied in the recorded assessment.

Benign criteria applied · 6

BA1Stand alone

BA1 · stand alone

The variant is present in gnomAD v2.1 at an allele frequency of 2.33% (grpmax filtering AF=10.84% in the African/African American population), far exceeding the BA1 threshold of >1%. A total of 307 homozygotes are observed in gnomAD v2.1. In gnomAD v4.1, AF=1.22% with 872 homozygotes. For an autosomal dominant disorder (Gorlin syndrome) with high penetrance, this frequency is incompatible with pathogenicity.

BS1Strong

BS1 · strong

The variant allele frequency of 2.33% in gnomAD v2.1 exceeds the BS1 threshold of >0.3% for a dominantly inherited disorder. This frequency alone is sufficient strong evidence for a benign classification, though it is subsumed by the stand-alone BA1 criterion.

BS2Strong

BS2 · strong

The variant is observed in the homozygous state in 307 individuals in gnomAD v2.1 and 872 in gnomAD v4.1. For PTCH1, which causes Gorlin syndrome (an autosomal dominant disorder with high penetrance and significant morbidity), observation of homozygosity in healthy population databases is incompatible with pathogenicity. A homozygous pathogenic PTCH1 variant would be expected to be lethal or cause severe disease.

BP4Supporting

BP4 · supporting

SpliceAI predicts no significant splicing impact (max delta score = 0.06, well below the clinically significant threshold of 0.1). Multiple in silico splicing prediction tools cited in the ClinVar submission concur that the variant does not affect normal splicing. This supports a benign interpretation for this synonymous variant.

BP6Supporting

BP6 · supporting

This variant is classified as Benign in ClinVar by 12 clinical diagnostic laboratories (Variation ID 255681), with criteria provided. Multiple submitters independently reached a benign classification, consistent with a reputable source classification for BP6.

BP7Supporting

BP7 · supporting

NM_000264.5:c.3141T>G is a synonymous variant (p.Leu1047=). SpliceAI predicts no splicing impact (max delta = 0.06, well below 0.1 threshold). The high population frequency (AF=2.33%) is inconsistent with evolutionary conservation at this position. These findings satisfy BP7 criteria for a synonymous variant with no predicted impact on splicing or protein function.

Recorded classification: Benign

gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BA1 stand-alone benign, BS1 strong benign, BS2 strong benign, BP4 supporting benign, BP6 supporting benign, BP7 supporting benign; combination = 1 stand-alone benign + 2 strong benign + 3 supporting benign, which maps to Benign.

02The sources

Evidence at a glance

Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.

gnomAD v4.1

gnomAD v2.1

Population frequency

19,701 / 1,614,126 alleles

gnomAD v4.1: 19,701 / 1,614,126 alleles. Recorded AF 0.0122054. Recorded homozygote count 872.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 0.0232868; MAF= 2.32868%, 6581/282606 alleles, homozygotes = 307) and has highest observed frequency in the African/African American population (AF= 0.113018; MAF= 11.30184%, 2818/24934 alleles, homozygotes = 163); grpmax FAF= 0.108406.

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.018894559669888154, 348/18418 alleles, homozygotes = 10).

Applied · BA1, BS1, BS2 →

gnomAD v4.1 ↗gnomAD v2.1 ↗gnomAD-Canada ↗

SpliceAI score

0.060 maximum delta

Recorded SpliceAI maximum delta score: 0.060. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · BP4, BP7 → SpliceAI ↗

ClinVar submissions

12 reported laboratory submissions

11 Benign · 1 benign.

Applied · BP6 → ClinVar ↗

Functional evidence

Statement recorded

OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.

No listed criterion applied OncoKB ↗

COSMIC

Cancer Hotspots

Somatic evidence

6 recorded samples

This variant has previously been reported in somatic cancers (COSMIC; COSV59476925, n = 6 times).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.

Context only

COSMIC ↗Cancer Hotspots ↗

For specialists

Technical detail

ACMG/AMP criteria under Not recorded, with the data and sources behind each one.

26 criteria with recorded statuses: 6 met · 7 not met · 8 not assessed · 5 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic

PVS1 PS1 PS2 PS3 PS4 PM1 PM2 PM5 PM6 PP1 PP2 PP3 PP4 PP5 PS5

Benign

BA1 BS1 BS2 BS3 BS4 BP1 BP2 BP4 BP5 BP6 BP7

Met Not met Not assessed Not applicable

NM_000264.5:c.3141T>G is a synonymous variant in PTCH1 present in gnomAD at an allele frequency of 2.33% with 307 homozygotes in v2.1, meeting BA1 (stand-alone benign) criterion.

The variant is classified as Benign in ClinVar by 12 clinical laboratories (Variation ID 255681), meeting BP6 (supporting benign).

As a synonymous variant with no predicted splice impact (SpliceAI max delta = 0.06), BP7 (supporting benign) is met.

Observation of 307 homozygotes in gnomAD v2.1 meets BS2 (strong benign); homozygous pathogenic PTCH1 variants are incompatible with viability in an autosomal dominant cancer predisposition syndrome.

Per the generic ACMG/AMP 2015 classification rules, a single BA1 (stand-alone benign) criterion is sufficient for a Benign classification, independent of other criteria.

The sole publication identifying this variant (Musani et al., 2013, PMID:23313819) described it as a rare polymorphism found in 1/28 ovarian carcinoma cases with no functional characterization, and concluded its frequency was too low to draw conclusions about a role in ovarian tumor development.

Met · 6

BA1 Stand aloneThe variant is present in gnomAD v2.1 at an allele frequency of 2.33% (grpmax filtering AF=10.84% in the African/African American population), far exceeding the BA1 threshold of >1%. A total of 307 homozygotes are observed in gnomAD v2.1. In gnomAD v4.1, AF=1.22% with 872 homozygotes. For an autosomal dominant disorder (Gorlin syndrome) with high penetrance, this frequency is incompatible with pathogenicity. Details ▾Hide ▴

Evidence considered

gnomAD v2.1: AF=2.33% (6581/282606 alleles)
307 homozygotes
grpmax FAF=0.1084
gnomAD v4.1: AF=1.22% (19701/1614126 alleles)
872 homozygotes
grpmax FAF=0.1123
African/African American AF=11.3% (v2.1)
11.4% (v4.1)

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS1 StrongThe variant allele frequency of 2.33% in gnomAD v2.1 exceeds the BS1 threshold of >0.3% for a dominantly inherited disorder. This frequency alone is sufficient strong evidence for a benign classification, though it is subsumed by the stand-alone BA1 criterion. Details ▾Hide ▴

Evidence considered

gnomAD v2.1: AF=2.33%
far exceeding 0.3% BS1 threshold
gnomAD v4.1: AF=1.22%
grpmax FAF=0.1084

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS2 StrongThe variant is observed in the homozygous state in 307 individuals in gnomAD v2.1 and 872 in gnomAD v4.1. For PTCH1, which causes Gorlin syndrome (an autosomal dominant disorder with high penetrance and significant morbidity), observation of homozygosity in healthy population databases is incompatible with pathogenicity. A homozygous pathogenic PTCH1 variant would be expected to be lethal or cause severe disease. Details ▾Hide ▴

Evidence considered

gnomAD v2.1: 307 homozygotes observed
gnomAD v4.1: 872 homozygotes observed
Gorlin syndrome is autosomal dominant with high penetrance
homozygous pathogenic variants would not be observed in healthy population databases

Sources

gnomad_v2 ↗gnomad_v4 ↗

BP4 SupportingSpliceAI predicts no significant splicing impact (max delta score = 0.06, well below the clinically significant threshold of 0.1). Multiple in silico splicing prediction tools cited in the ClinVar submission concur that the variant does not affect normal splicing. This supports a benign interpretation for this synonymous variant. Details ▾Hide ▴

Evidence considered

SpliceAI max delta = 0.06 (no predicted splicing impact)
LabCorp ClinVar submission: 5/5 in silico splicing programs predict no effect

Sources

spliceai ↗

BP6 SupportingThis variant is classified as Benign in ClinVar by 12 clinical diagnostic laboratories (Variation ID 255681), with criteria provided. Multiple submitters independently reached a benign classification, consistent with a reputable source classification for BP6. Details ▾Hide ▴

Evidence considered

ClinVar Variation ID 255681: Benign (12 clinical laboratories)
Review status: criteria provided
single submitter
Submitters include Invitae
GeneDx
Ambry Genetics
Mayo Clinic
LabCorp
and others

Sources

clinvar ↗

BP7 SupportingNM_000264.5:c.3141T>G is a synonymous variant (p.Leu1047=). SpliceAI predicts no splicing impact (max delta = 0.06, well below 0.1 threshold). The high population frequency (AF=2.33%) is inconsistent with evolutionary conservation at this position. These findings satisfy BP7 criteria for a synonymous variant with no predicted impact on splicing or protein function. Details ▾Hide ▴

Evidence considered

Synonymous variant p.Leu1047= with no amino acid change
SpliceAI max delta = 0.06 (no predicted splicing impact)
High population frequency (AF=2.33%) indicates lack of evolutionary constraint

Sources

spliceai ↗gnomad_v2 ↗

Not met · 7 · evaluated, threshold not reached

PS3 No well-established functional studies demonstrate a damaging effect for NM_000264.5:c.3141T>G. The one study that identified the variant (Musani et al., 2013) described it as a rare polymorphism with no functional characterization. The variant's high population frequency further argues against a damaging functional effect. Details ▾Hide ▴

Evidence considered

Musani et al. 2013 identified c.3141T>G in 1/28 ovarian carcinoma cases and classified it as a rare polymorphism
with no functional data
gnomAD: AF=2.33% with 307 homozygotes — incompatible with a damaging functional effect

Sources

PMID:23313819 ↗

PS4 The variant is common in the general population (gnomAD v2.1 AF=2.33%, 307 homozygotes), making it statistically incompatible with significant enrichment in affected individuals. PS4 requires significantly increased prevalence in cases versus controls. Details ▾Hide ▴

Evidence considered

gnomAD v2.1: AF=2.33%
6581/282606 alleles
307 homozygotes
gnomAD v4.1: AF=1.22%
19701/1614126 alleles
872 homozygotes
Variant far too common to be enriched in a rare autosomal dominant disorder (Gorlin syndrome)

Sources

gnomad_v2 ↗gnomad_v4 ↗

PM1 The variant does not lie in a statistically significant mutational hot spot in PTCH1. Evidence from cancer hotspot databases confirms c.3141T>G is not in a recognized functional domain hot spot. Details ▾Hide ▴

Evidence considered

Hotspots analysis: residue_significant=false
exact_variant_listed=no

PM2 The variant is present in gnomAD at high frequency (AF=2.33% in v2.1, 307 homozygotes), far exceeding the PM2 absence threshold of <0.1%. This criterion is clearly not met. Details ▾Hide ▴

Evidence considered

gnomAD v2.1: AF=2.33% (6581/282606 alleles)
gnomAD v4.1: AF=1.22% (19701/1614126 alleles)

Sources

gnomad_v2 ↗gnomad_v4 ↗

PP3 SpliceAI predicts no significant splicing impact (max delta score = 0.06). REVEL and BayesDel scores are unavailable. No in silico evidence supports a deleterious effect for this synonymous variant. Details ▾Hide ▴

Evidence considered

SpliceAI max delta = 0.06 (no predicted splicing impact)
REVEL score: not available
BayesDel score: not available

Sources

spliceai ↗

PP5 ClinVar classifies this variant as Benign by 12 clinical laboratories, not pathogenic. PP5 requires a reputable source to have recently classified the variant as pathogenic. Details ▾Hide ▴

Evidence considered

ClinVar Variation ID 255681: Benign classification by 12 submitters
No expert panel or reputable source classifies this variant as pathogenic

Sources

clinvar ↗

PS5 ClinVar classifies this variant as Benign (12 clinical laboratories, criteria provided). No reputable source has recently classified it as pathogenic. PS5 requires a reputable source to report the variant as pathogenic. Details ▾Hide ▴

Evidence considered

ClinVar Variation ID 255681: Benign (11 labs)
benign (1 lab)
review status: criteria provided
single submitter

Sources

clinvar ↗

Not assessed · 8 · no assessment recorded

PS2 No de novo data are available for this variant. PS2 requires confirmed de novo occurrence in a patient with the disease and no family history. Details ▾Hide ▴

Still missing

No de novo data identified

PM6 No de novo data are available for this variant. PM6 requires a de novo observation without confirmation of paternity and maternity. Details ▾Hide ▴

Still missing

No de novo data identified

PP1 No cosegregation data are available for this variant. PP1 requires cosegregation of the variant with disease in multiple affected family members. Details ▾Hide ▴

Still missing

No cosegregation data identified

PP4 No data on the patient's phenotype or family history are available. PP4 requires a highly specific phenotype for the disease with a single genetic etiology. Details ▾Hide ▴

Still missing

No phenotype data available

BS3 No well-established functional studies directly demonstrate that NM_000264.5:c.3141T>G has no damaging effect on protein function or splicing. The ClinVar submission from LabCorp notes that 5/5 in silico programs predict no splicing effect, but no formal functional studies were published. The extreme population frequency, however, serves as strong indirect evidence of no functional impact. Details ▾Hide ▴

Evidence considered

LabCorp ClinVar submission (SCV000696377): 5/5 splicing programs predict no effect
no published functional studies

Still missing

No direct functional study of this variant

BS4 No segregation data are available for this variant. BS4 requires lack of cosegregation in affected family members. Details ▾Hide ▴

Still missing

No segregation data available

BP2 No data are available regarding observation of this variant in trans with a known pathogenic PTCH1 variant. BP2 requires observation in trans with a pathogenic variant for a dominantly inherited disorder. Details ▾Hide ▴

Still missing

No data on co-occurrence with pathogenic PTCH1 variants

BP5 No data are available regarding an alternate molecular basis for disease in individuals carrying this variant. BP5 requires identification of an alternative causative variant in a case where this variant was also found. Details ▾Hide ▴

Still missing

No alternate molecular basis data available

Not applicable · 5· recorded as not applicable Show reasons ▾Hide reasons ▴

PVS1 N/ANM_000264.5:c.3141T>G is a synonymous variant (p.Leu1047=) that does not alter the protein sequence. PVS1 is reserved for null variants (nonsense, frameshift, canonical ±1/2 splice sites) and is not applicable to synonymous substitutions. Details ▾Hide ▴

Evidence considered

Synonymous substitution p.Leu1047= produces no amino acid change
Variant bucket: other
not a null variant per ClinGen SVI PVS1 framework

Sources

pvs1_gene_contextpvs1_variant_assessment

PS1 N/APS1 applies when the variant produces the same amino acid change as a previously established pathogenic variant. NM_000264.5:c.3141T>G is synonymous (p.Leu1047=) and produces no amino acid change, rendering this criterion inapplicable. Details ▾Hide ▴

Evidence considered

Synonymous variant
no amino acid change to compare

PM5 N/APM5 applies when a novel missense change occurs at the same residue as a known pathogenic missense variant. NM_000264.5:c.3141T>G is a synonymous variant and does not alter the amino acid at position 1047. Details ▾Hide ▴

Evidence considered

Synonymous variant p.(Leu1047=)
PM5 not applicable to synonymous substitutions

Sources

pm5_candidates

PP2 N/APP2 applies to missense variants in genes with a low rate of benign missense variation. NM_000264.5:c.3141T>G is synonymous (p.Leu1047=), not a missense change. Details ▾Hide ▴

Evidence considered

Synonymous variant
PP2 requires missense

BP1 N/ABP1 applies to missense variants in genes where only truncating variants cause disease. NM_000264.5:c.3141T>G is synonymous, not missense. Details ▾Hide ▴

Evidence considered

Synonymous variant
BP1 requires missense

Identifiers

Gene: PTCH1
Transcript: NM_000264.5
Coding (HGVS c.): NM_000264.5:c.3141T>G
Protein (HGVS p.): NP_000255.2:p.(Leu1047=)
GRCh38: chr9:95458040 A>C
GRCh37: chr9:98220322 A>C
ClinVar: 255681
COSMIC: COSV59476925

Gene diagram

Every interpreted variant in PTCH1, mapped onto the exon structure of NM_000264.5. Select a row to find it on the plot.

PTCH1NM_000264.5

Fetching transcript structure from UCSC…

Exons

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Transcript span

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Strand

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Variants mapped

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Source

UCSC ncbiRefSeqCurated

All variants in PTCH1 — Select a row to find it on the plot; use the link to open its page.

	Protein	Location	Classification	Link

gnomAD v4.1 19,701 / 1,614,126 alleles AF 0.0122 · 872 homozygotes · FAF 0.112

gnomAD v2.1 6,581 / 282,606 alleles AF 0.0233 · 307 homozygotes · FAF 0.108

gnomAD-Canada v1.0 Allele count data not recorded

By genetic ancestry

gnomAD v4.1

AF 0.012 · 19701 / 1,614,126 alleles · 872 hom · FAF 0.11

African/African American8580 / 75,026	0.11500 hom
East Asian4252 / 44,876	0.095223 hom
South Asian3918 / 91,088	0.043113 hom
Remaining individuals1023 / 62,510	0.01627 hom
Middle Eastern58 / 6,060	0.00961 hom
Admixed American449 / 60,024	0.00758 hom
European (non-Finnish)1401 / 1,180,030	0.0012
Ashkenazi Jewish16 / 29,606	0.00054
European (Finnish)4 / 63,994	6.3e-05

0 alternate alleles recorded in 1 other group: Amish.

gnomAD v2.1

AF 0.023 · 6581 / 282,606 alleles · 307 hom · FAF 0.11

African/African American2818 / 24,934	0.11163 hom
East Asian2025 / 19,944	0.1104 hom
South Asian1327 / 30,610	0.04337 hom
Remaining individuals69 / 7,220	0.00961 hom
Admixed American177 / 35,434	0.0052 hom
European (non-Finnish)161 / 128,988	0.0012
Ashkenazi Jewish3 / 10,354	0.00029
European (Finnish)1 / 25,122	4e-05

gnomAD-Canada

AF not recorded · ? / ? alleles

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 0.0122054; MAF= 1.22054%, 19701/1614126 alleles, homozygotes = 872) and has highest observed frequency in the African/African American population (AF= 0.11436; MAF= 11.43604%, 8580/75026 alleles, homozygotes = 500); grpmax FAF= 0.112337.

gnomAD v2.1

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.018894559669888154, 348/18418 alleles, homozygotes = 10).

Open the gnomAD-Canada detail page →

SpliceAI and Pangolin

SpliceAI acceptor lossat +18 bp

0.000

SpliceAI acceptor gainat +80 bp

0.000

SpliceAI donor lossat +162 bp

0.060

SpliceAI donor gainat -27 bp

0.000

Pangolin splice lossmagnitude shown

-0.020

Pangolin splice gain

0.010

Other predictors

REVEL: Not available
BayesDel: Not available

How the predictions were used

Evidence considered

SpliceAI max delta = 0.06 (no predicted splicing impact)
LabCorp ClinVar submission: 5/5 in silico splicing programs predict no effect

Sources

spliceai ↗

Evidence considered

Synonymous variant p.Leu1047= with no amino acid change
SpliceAI max delta = 0.06 (no predicted splicing impact)
High population frequency (AF=2.33%) indicates lack of evolutionary constraint

Sources

spliceai ↗gnomad_v2 ↗

Evidence considered

SpliceAI max delta = 0.06 (no predicted splicing impact)
REVEL score: not available
BayesDel score: not available

Sources

spliceai ↗

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.06).

9 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.

Recorded publications

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

This is the ACMG/AMP 2015 standards and guidelines for variant interpretation. It defines the classification criteria framework but does not evaluate or mention any specific variant.
Does not name this variant
PMID 25741868 ↗
A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Describes a standardized DNA variant scoring system for Mendelian disorders. The abstract discusses a rules-based pathogenicity classification system applied to over 11,894 variants across 338 genes. No specific PTCH1 variants are mentioned.
Does not name this variant
PMID 26467025 ↗
Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors.

Trepanier A et al. · 2004

National Society of Genetic Counselors practice recommendations for cancer genetic risk assessment and counseling. Provides general guidance on identifying at-risk individuals. No specific PTCH1 variants are discussed.
Does not name this variant
PMID 15604628 ↗
PTCH1 and SMO gene alterations in keratocystic odontogenic tumors.

Sun LS et al. · 2008

Study of PTCH1 and SMO gene alterations in keratocystic odontogenic tumors. Investigated PTCH1 mutations in KCOTs associated with nevoid basal cell carcinoma syndrome. Abstract does not mention c.3141T>G specifically, though the Musani et al. 2013 study cites this paper as one of three prior reports of the variant.
Does not name this variant
PMID 18502968 ↗
Clinical utility gene card for: Gorlin syndrome.

Lo Muzio L et al. · 2011

Clinical utility gene card for Gorlin syndrome. Summarizes PTCH1 gene characteristics, mutation spectrum, and clinical testing recommendations. No specific variants are evaluated.
Does not name this variant
PMID 21304560 ↗
PTCH1 gene polymorphisms in ovarian tumors: potential protective role of c.3944T allele.

Musani V et al. · 2013

c.3141T>G identified as a rare synonymous polymorphism (p.Leu1047=) in 1 of 28 ovarian carcinoma cases. Absent from 19 dermoid, 14 fibroma, and 30 healthy control samples. Described as a rare polymorphism previously reported in only three studies, with frequency too low to draw conclusions regarding a role in ovarian tumor development.
Names this variant
PMID 23313819 ↗
Quoted passage
The other polymorphism, c.3141T>G, found in only one OC sample, is a rare polymorphism previously described in only three reports (Evans et al., 2000; Hasenpusch-Theil et al., 1998; Sun et al., 2008), and its frequency is too low to draw any conclusions regarding its role in ovarian tumor development.
Table 1; Results section 3.3, paragraph 5; Discussion, line 540-544
A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.

Hampel H et al. · 2015

ACMG/NSGC practice guideline for referral indications for cancer predisposition assessment. Provides clinical criteria for genetic counseling referral. Does not discuss specific PTCH1 variants.
Does not name this variant
PMID 25394175 ↗
Cancer Genetics Risk Assessment and Counseling (PDQ®): Health Professional Version.

PDQ Cancer Genetics Editorial Board · 2002

PDQ Cancer Genetics Risk Assessment and Counseling summary. Provides general clinical guidance on hereditary cancer syndromes. No specific PTCH1 variants are discussed.
Does not name this variant
PMID 26389258 ↗
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Sherloc refinement of the ACMG-AMP variant classification criteria. Describes a comprehensive framework for variant interpretation. No specific PTCH1 variants are mentioned.
Does not name this variant
PMID 28492532 ↗

Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.

gnomAD v4.1 19,701 / 1,614,126 recorded alleles Open source ↗

gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗

SpliceAI Lookup Recorded maximum delta 0.060 Open source ↗

ClinVar 11 Benign · 1 benign Open source ↗

COSMIC Captured COSMIC source record Open source ↗

Cancer hotspots Captured Cancer Hotspots source record Open source ↗

OncoKB Captured OncoKB source record Open source ↗

All source links

Statements for reports

The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.

gnomAD v4.1

gnomAD v2.1

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.018894559669888154, 348/18418 alleles, homozygotes = 10).

ClinVar

This variant has been reported in ClinVar as Benign (11 clinical laboratories) and as benign (1 clinical laboratory). (ClinVarID = 255681)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.06).

Functional

OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.

Somatic

This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV59476925, n = 6 times).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.