TSC1c.2194C>TLikely benign

Print report

Variant interpretation report

TSC1 c.2194C>T, p.(His732Tyr)

NM_000368.5:c.2194C>T NP_000359.1:p.(His732Tyr) View identifiers

Classification

Likely benign

Variant description:

No variant summary was recorded for this case.

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

Likely benign.A likely benign classification under the recorded framework.

In plain language

Gene-level background from the recorded interpretation.

About TSC1

No gene-level summary was recorded for this case.

Key facts

Evidence used: 1 strong (benign) · 2 supporting (benign)
Expert rules: Not recorded
Other laboratories (ClinVar): 23 Benign · 4 Likely benign
Pipeline record: 17 Jun 2026

Evidence considered

View criteria

Applied evidence criteria

BS1 (strong): The variant is present in gnomAD v2.1 at AF 0.387% (1093/282512 alleles, 7 homozygotes) and gnomAD v4.1 at AF 0.360% (5806/1612416 alleles, 28 homozygotes). Both overall frequencies exceed the 0.3% BS1 threshold. The presence of 7–28 apparently healthy homozygous individuals in population databases for an autosomal dominant tumor suppressor gene (TSC1) provides strong evidence that this variant is benign. PMID:19918125 independently reported the allele at 0.5% in the normal population and concluded it 'cannot be sufficient to cause TSC or FCD.'
BP4 (supporting): Multiple in silico predictors consistently indicate a benign impact. REVEL score is 0.338 (below the 0.5 threshold for pathogenic prediction), BayesDel score is -0.064 (negative, favoring benign), and SpliceAI max delta is 0.09 (below the 0.2 threshold for splicing impact). All three orthogonal computational tools agree on a benign/non-damaging prediction.
BP6 (supporting): This variant is classified as Benign in ClinVar by 23 clinical laboratories and as Likely benign by 4 clinical laboratories (ClinVar Variation ID: 5103). The review status is 'criteria provided, single submitter.' The strong clinical consensus — 23 out of 27 classified submissions are 'Benign' — supports a benign interpretation under BP6.

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: 3

Pathogenic criteria applied · 0

No pathogenic criterion marked as applied in the recorded assessment.

Benign criteria applied · 3

BS1Strong

BS1 · strong

The variant is present in gnomAD v2.1 at AF 0.387% (1093/282512 alleles, 7 homozygotes) and gnomAD v4.1 at AF 0.360% (5806/1612416 alleles, 28 homozygotes). Both overall frequencies exceed the 0.3% BS1 threshold. The presence of 7–28 apparently healthy homozygous individuals in population databases for an autosomal dominant tumor suppressor gene (TSC1) provides strong evidence that this variant is benign. PMID:19918125 independently reported the allele at 0.5% in the normal population and concluded it 'cannot be sufficient to cause TSC or FCD.'

BP4Supporting

BP4 · supporting

Multiple in silico predictors consistently indicate a benign impact. REVEL score is 0.338 (below the 0.5 threshold for pathogenic prediction), BayesDel score is -0.064 (negative, favoring benign), and SpliceAI max delta is 0.09 (below the 0.2 threshold for splicing impact). All three orthogonal computational tools agree on a benign/non-damaging prediction.

BP6Supporting

BP6 · supporting

This variant is classified as Benign in ClinVar by 23 clinical laboratories and as Likely benign by 4 clinical laboratories (ClinVar Variation ID: 5103). The review status is 'criteria provided, single submitter.' The strong clinical consensus — 23 out of 27 classified submissions are 'Benign' — supports a benign interpretation under BP6.

Recorded classification: Likely 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: BS1 strong, BP4 supporting benign, BP6 supporting benign; combination = 1 strong benign + 2 supporting benign, which maps to Likely 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

5,806 / 1,612,416 alleles

gnomAD v4.1: 5,806 / 1,612,416 alleles. Recorded AF 0.00360081. Recorded homozygote count 28.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 0.00386886; MAF= 0.38689%, 1093/282512 alleles, homozygotes = 7) and has highest observed frequency in the European (Finnish) population (AF= 0.0138159; MAF= 1.38159%, 347/25116 alleles, homozygotes = 3); grpmax FAF= 0.00616893.

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.002062975027144408, 38/18420 alleles, homozygotes = 0).

Applied · BS1 →

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

SpliceAI score

0.090 maximum delta

Recorded SpliceAI maximum delta score: 0.090. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · BP4 → SpliceAI ↗

ClinVar submissions

27 reported laboratory submissions

23 Benign · 4 Likely benign.

Applied · BP6 → ClinVar ↗

Functional evidence

Statement recorded

OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. TSC1, a scaffold protein, is frequently altered by mutation in bladder cancer.

No listed criterion applied OncoKB ↗

COSMIC

Cancer Hotspots

Somatic evidence

6 recorded samples

This variant has previously been reported in somatic cancers (COSMIC; COSV104404438, 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.

27 criteria with recorded statuses: 3 met · 11 not met · 7 not assessed · 6 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 BP3 BP4 BP5 BP6 BP7

Met Not met Not assessed Not applicable

NM_000368.5:c.2194C>T (p.His732Tyr) is a missense variant in TSC1, a gene in which loss-of-function variants cause tuberous sclerosis complex (autosomal dominant).

The variant is present in gnomAD v2.1 at an allele frequency of 0.387% (1093/282512 alleles) with 7 homozygotes, and in gnomAD v4.1 at 0.360% (5806/1612416 alleles) with 28 homozygotes. This frequency exceeds the 0.3% threshold for BS1 (strong benign).

The presence of 28 homozygous individuals in gnomAD v4.1 is incompatible with a highly penetrant autosomal dominant tumor suppressor disorder; homozygous loss of TSC1 function would be expected to cause severe disease.

Multiple in silico predictors support a benign interpretation: REVEL score 0.338 (below 0.5 pathogenic threshold), BayesDel score -0.064 (negative score), and SpliceAI max delta 0.09 (below 0.2 splicing threshold), meeting BP4 (supporting benign).

In ClinVar, 23 clinical laboratories classify this variant as Benign and 4 as Likely benign (Variation ID: 5103), meeting BP6 (supporting benign).

PMID:19918125 (Lugnier et al. 2009) characterized hamartin H732Y in vitro and demonstrated reduced tuberin binding (2.3-fold, p<0.05) and aberrant nuclear localization. However, the paper explicitly reported the allele at 0.5% frequency in the normal population and concluded it 'cannot be sufficient to cause TSC or FCD,' describing it as a low-penetrance predisposing variant at most.

Applying generic ACMG/AMP 2015 combination rules (PMID:25741868): one strong benign criterion (BS1) plus two supporting benign criteria (BP4, BP6) yields a final classification of Likely Benign.

Met · 3

BS1 StrongThe variant is present in gnomAD v2.1 at AF 0.387% (1093/282512 alleles, 7 homozygotes) and gnomAD v4.1 at AF 0.360% (5806/1612416 alleles, 28 homozygotes). Both overall frequencies exceed the 0.3% BS1 threshold. The presence of 7–28 apparently healthy homozygous individuals in population databases for an autosomal dominant tumor suppressor gene (TSC1) provides strong evidence that this variant is benign. PMID:19918125 independently reported the allele at 0.5% in the normal population and concluded it 'cannot be sufficient to cause TSC or FCD.' Details ▾Hide ▴

Evidence considered

gnomAD v2.1 AF=0.387% with 7 homozygotes
gnomAD v4.1 AF=0.360% with 28 homozygotes
PMID:19918125 reports 0.5% in normal population and explicitly states variant cannot cause TSC

Sources

gnomad_v2 ↗gnomad_v4 ↗PMID:19918125 ↗19918125

BP4 SupportingMultiple in silico predictors consistently indicate a benign impact. REVEL score is 0.338 (below the 0.5 threshold for pathogenic prediction), BayesDel score is -0.064 (negative, favoring benign), and SpliceAI max delta is 0.09 (below the 0.2 threshold for splicing impact). All three orthogonal computational tools agree on a benign/non-damaging prediction. Details ▾Hide ▴

Evidence considered

REVEL=0.338 (<0.5)
BayesDel=-0.064 (negative score)
SpliceAI delta=0.09 (<0.2)

Sources

revelbayesdelspliceai ↗

BP6 SupportingThis variant is classified as Benign in ClinVar by 23 clinical laboratories and as Likely benign by 4 clinical laboratories (ClinVar Variation ID: 5103). The review status is 'criteria provided, single submitter.' The strong clinical consensus — 23 out of 27 classified submissions are 'Benign' — supports a benign interpretation under BP6. Details ▾Hide ▴

Evidence considered

ClinVar: Benign (23 labs)
Likely benign (4 labs)
Variation ID 5103

Sources

clinvar ↗

Not met · 11 · evaluated, threshold not reached

PS2 One confirmed de novo occurrence reported (PMID:17304050) in a TSC proband with confirmed parental testing, but PS2 requires ≥2 de novo observations for strong evidence. A single de novo case is insufficient to meet PS2, especially given the variant is common in population databases (gnomAD AF 0.37%, 7–28 homozygotes). Details ▾Hide ▴

Evidence considered

One confirmed de novo case reported in PMID:17304050 per exploratory review
insufficient to meet threshold

Still missing

Only a single de novo case identified
additional independent de novo observations would be needed

PS3 PMID:19918125 (Lugnier et al. 2009) characterized hamartin H732Y in vitro: coimmunoprecipitation assays demonstrated 2.3-fold reduced tuberin binding (p<0.05, n=9 replicates), and the variant showed aberrant nuclear localization in HEK293T cells. However, the paper explicitly states this allele is present in 0.5% of the normal population and 'cannot be sufficient to cause TSC or FCD.' PS3 requires well-established functional studies showing a damaging effect in a disease-relevant context; the in vitro impairment is present but the variant's high population frequency and the authors' own conclusion that it is not disease-causing preclude application of PS3. Details ▾Hide ▴

Evidence considered

Reduced tuberin binding (2.3-fold
p<0.05) and aberrant nuclear localization in HEK293T cells
but the paper concludes this variant is found in normal population and cannot cause TSC

Still missing

Functional data show partial impairment but paper itself notes the variant is common in unaffected individuals

Sources

PMID:19918125 ↗19918125

PS4 The variant has been observed in TSC patient cohorts (1/325 probands in PMID:17304050; also reported in PMID:15798777), but the prevalence in affected individuals does not significantly exceed the general population frequency of ~0.37% (gnomAD). No formal case-control study with a statistically significant odds ratio has been conducted. Details ▾Hide ▴

Evidence considered

Observed in 1/325 TSC probands (PMID:17304050)
variant is present at 0.37% in gnomAD
so prevalence in cases is not enriched above population background

Still missing

No formal case-control study comparing variant frequency in affected vs unaffected populations

Sources

gnomad_v2 ↗gnomad_v4 ↗

PM1 Residue His732 lies outside the well-established TSC1 functional domains. The N-terminal TSC2-binding domain spans amino acids 1–266 and the C-terminal coiled-coil tuberin-binding domain spans amino acids 881–1084 (PMID:9580671). His732 is not in a critical functional domain, a recognized mutational hotspot, or a region where pathogenic missense variants are enriched. Details ▾Hide ▴

Evidence considered

Residue 732 is outside known TSC2-binding domains (aa 1–266
881–1084 per PMID:9580671)
not in a mutational hotspot

PM2 The variant is present in gnomAD v2.1 at AF 0.00387 (0.387%, 1093/282512 alleles, 7 homozygotes) and in gnomAD v4.1 at AF 0.00360 (0.360%, 5806/1612416 alleles, 28 homozygotes). Both frequencies exceed the 0.1% threshold for PM2. The variant is common, not rare. Details ▾Hide ▴

Evidence considered

gnomAD v2.1 AF=0.387%
gnomAD v4.1 AF=0.360%
both >0.1% threshold

Sources

gnomad_v2 ↗gnomad_v4 ↗

PM6 One presumed de novo occurrence without confirmation of paternity/maternity was reported (PMID:15798777). However, PM6 requires ≥2 independent assumed de novo events to reach moderate strength, and the variant's high population frequency (gnomAD AF 0.37%) makes a de novo interpretation unreliable. A single presumed de novo in the context of a common population variant does not meet PM6. Details ▾Hide ▴

Evidence considered

One presumed de novo case without parental confirmation (PMID:15798777)
insufficient given high population frequency

Still missing

Insufficient de novo observations
variant is too common in population for de novo interpretation to be reliable

Sources

gnomad_v2 ↗gnomad_v4 ↗

PP3 Multiple in silico predictors suggest a benign impact: REVEL score 0.338 (threshold ≥0.5 for pathogenic), BayesDel score -0.064 (threshold >0 for pathogenic), SpliceAI max delta 0.09 (threshold ≥0.2 for splice effect). No computational evidence supports a deleterious effect. Details ▾Hide ▴

Evidence considered

REVEL=0.338 (<0.5)
BayesDel=-0.064 (<0)
SpliceAI max delta=0.09 (<0.2)

Sources

revelbayesdelspliceai ↗

PP5 ClinVar classification for this variant is Benign (23 clinical laboratories) and Likely benign (4 laboratories); PP5 is applicable only when reputable sources classify the variant as pathogenic. The consensus benign classification precludes PP5. Details ▾Hide ▴

Evidence considered

ClinVar classification is Benign (23 labs) / Likely benign (4 labs)
PP5 requires a pathogenic assertion

Sources

clinvar ↗

BA1 The overall gnomAD allele frequency is 0.37% (v2.1) and 0.36% (v4.1), which is below the 1% BA1 threshold. Although the Finnish subpopulation frequency reaches 1.38% (v2.1) with 3 homozygotes, the grpmax filtering allele frequency (upper bound of 95% CI for the highest subpopulation) is 0.62% (v2.1) and 0.38% (v4.1) — below 1%. Using the conservative grpmax FAF metric, BA1 is not met. However, BS1 is met (see below). Details ▾Hide ▴

Evidence considered

Overall AF=0.37% (<1%)
grpmax FAF=0.62% (<1%)
Finnish raw AF=1.38% noted but does not meet BA1 under conservative grpmax framework

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS3 No well-established functional studies demonstrate that the H732Y variant has no damaging effect on protein function. The available functional data (PMID:19918125) shows reduced tuberin binding and aberrant nuclear localization — a partially impaired phenotype, not a benign functional result. BS3 requires functional evidence showing no deleterious impact. Details ▾Hide ▴

Evidence considered

PMID:19918125 shows reduced tuberin binding (2.3-fold
p<0.05) — not a benign functional result
no benign functional studies exist

Still missing

No functional studies demonstrating benign effect are available

Sources

PMID:19918125 ↗19918125

BP1 BP1 is applicable to missense variants in genes where primarily truncating variants cause disease. While TSC1 disease mechanism is loss-of-function, numerous pathogenic missense variants are also well-documented in TSC1. The gene does not have a predominantly truncating pathogenic variant spectrum, so BP1 does not apply. Details ▾Hide ▴

Evidence considered

TSC1 has both truncating and missense pathogenic variants
not a predominantly truncating disease mechanism

Not assessed · 7 · no assessment recorded

PS1 No known pathogenic variant resulting in the same amino acid change (His732Tyr) was identified. PS1 requires a previously classified pathogenic variant at the same residue with an identical predicted amino acid consequence. Details ▾Hide ▴

Still missing

No pathogenic comparator at His732 with the same His→Tyr change is catalogued

PP1 No published cosegregation data are available for this variant in families with multiple affected individuals. Cosegregation with disease in ≥3–4 affected family members would be needed to apply PP1. Details ▾Hide ▴

Still missing

No family cosegregation studies published for this variant

PP4 PP4 requires detailed patient phenotype information and specificity scoring; insufficient phenotype data are available to assess whether the variant is enriched in patients with a phenotype highly specific for TSC1-related disease. Details ▾Hide ▴

Still missing

Detailed phenotype data not available for systematic PP4 assessment

BS2 BS2 (observed in a healthy adult individual for a fully penetrant disorder) is superseded by BS1, which provides stronger population-based evidence using allele frequency rather than individual observations. Details ▾Hide ▴

No further detail was recorded.

BS4 No published reports demonstrate lack of segregation of this variant with disease in affected families. The strong population evidence (BS1) provides comparable weight to BS4. Details ▾Hide ▴

Still missing

No systematic family segregation studies for this variant

BP5 BP5 requires an alternate molecular basis for disease in a case where the variant is observed. No such data were identified for this case; the strong population evidence (BS1) is the primary benign criterion. Details ▾Hide ▴

No further detail was recorded.

PS5 No alternate pathogenic variant at the same nucleotide position (c.2194) has been identified and classified as pathogenic. PS5 requires a different nucleotide change at the same position with an established pathogenic classification. Details ▾Hide ▴

Still missing

No alternate pathogenic nucleotide change at c.2194 is catalogued

Not applicable · 6· recorded as not applicable Show reasons ▾Hide reasons ▴

PVS1 N/ANM_000368.5:c.2194C>T is a missense variant (p.His732Tyr); PVS1 is applicable only to null variants (nonsense, frameshift, canonical ±1,2 splice sites, initiation codon, single/multi-exon deletions). This variant does not fall into any null-variant bucket. Details ▾Hide ▴

Evidence considered

Missense substitution at codon 732
not a null variant

Sources

pvs1_generic_framework ↗pvs1_variant_assessment

PM5 N/ANo same-residue comparator variants with a different pathogenic amino acid change could be confirmed by automated candidate harvesting. Classic PM5 semantics could not be established. Details ▾Hide ▴

Evidence considered

No qualifying same-residue (His732) comparator variants identified

Sources

pm5_candidates

PP2 N/APP2 applies to genes where missense variants are a common mechanism of disease and the gene has a low rate of benign missense variation (high missense Z-score). TSC1 has a missense Z-score that does not meet the threshold for PP2, and the variant is common in population databases. Details ▾Hide ▴

Evidence considered

TSC1 missense constraint metrics do not support PP2 applicability

BP2 N/ABP2 applies to variants observed in trans with a pathogenic variant in a fully penetrant recessive disorder. TSC1-related tuberous sclerosis complex is an autosomal dominant condition; BP2 is not applicable. Details ▾Hide ▴

No further detail was recorded.

BP3 N/ASkipped: in-frame deletions/insertions in repetitive regions are not applicable to this missense substitution variant. Details ▾Hide ▴

No further detail was recorded.

BP7 N/ABP7 applies to synonymous (silent) variants predicted not to affect splicing. c.2194C>T is a missense variant (p.His732Tyr), not a synonymous variant. Details ▾Hide ▴

No further detail was recorded.

Identifiers

Gene: TSC1
Transcript: NM_000368.5
Coding (HGVS c.): NM_000368.5:c.2194C>T
Protein (HGVS p.): NP_000359.1:p.(His732Tyr)
GRCh38: chr9:132903665 G>A
GRCh37: chr9:135779052 G>A
ClinVar: 1719479, 48942, 5103
COSMIC: COSV104404438

Gene diagram

Every interpreted variant in TSC1, mapped onto the exon structure of NM_000368.5. Select a row to find it on the plot.

TSC1NM_000368.5

Fetching transcript structure from UCSC…

Exons

—

Transcript span

—

Strand

—

Variants mapped

—

Source

UCSC ncbiRefSeqCurated

All variants in TSC1 — Select a row to find it on the plot; use the link to open its page.

	Protein	Location	Classification	Link

gnomAD v4.1 5,806 / 1,612,416 alleles AF 0.0036 · 28 homozygotes · FAF 0.00382

gnomAD v2.1 1,093 / 282,512 alleles AF 0.00387 · 7 homozygotes · FAF 0.00617

gnomAD-Canada v1.0 Allele count data not recorded

By genetic ancestry

gnomAD v4.1

AF 0.0036 · 5806 / 1,612,416 alleles · 28 hom · FAF 0.0038

European (Finnish)896 / 64,030	0.01411 hom
European (non-Finnish)4619 / 1,179,952	0.003916 hom
Remaining individuals183 / 62,348	0.00291 hom
Admixed American66 / 60,028	0.0011
African/African American40 / 74,996	0.00053
Ashkenazi Jewish1 / 29,604	3.4e-05
South Asian1 / 91,000	1.1e-05

0 alternate alleles recorded in 3 other groups: Amish, East Asian, Middle Eastern.

gnomAD v2.1

AF 0.0039 · 1093 / 282,512 alleles · 7 hom · FAF 0.0062

European (Finnish)347 / 25,116	0.0143 hom
European (non-Finnish)650 / 128,862	0.0054 hom
Remaining individuals32 / 7,210	0.0044
Admixed American43 / 35,436	0.0012
African/African American21 / 24,964	0.00084

0 alternate alleles recorded in 3 other groups: Ashkenazi Jewish, East Asian, South Asian.

gnomAD-Canada

AF not recorded · ? / ? alleles

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 0.00360081; MAF= 0.36008%, 5806/1612416 alleles, homozygotes = 28) and has highest observed frequency in the European (Finnish) population (AF= 0.0139934; MAF= 1.39934%, 896/64030 alleles, homozygotes = 11); grpmax FAF= 0.00382016.

gnomAD v2.1

gnomAD-Canada

This variant is present in gnomAD-Canada v1.0 (AF= 0.002062975027144408, 38/18420 alleles, homozygotes = 0).

Open the gnomAD-Canada detail page →

SpliceAI and Pangolin

SpliceAI acceptor lossat -139 bp

0.000

SpliceAI acceptor gainat +152 bp

0.000

SpliceAI donor lossat -14 bp

0.000

SpliceAI donor gainat +28 bp

0.090

Pangolin splice lossmagnitude shown

-0.000

Pangolin splice gain

0.070

Other predictors

REVEL: 0.338
BayesDel: -0.064

How the predictions were used

Evidence considered

REVEL=0.338 (<0.5)
BayesDel=-0.064 (negative score)
SpliceAI delta=0.09 (<0.2)

Sources

revelbayesdelspliceai ↗

Evidence considered

REVEL=0.338 (<0.5)
BayesDel=-0.064 (<0)
SpliceAI max delta=0.09 (<0.2)

Sources

revelbayesdelspliceai ↗

BP7 N/ABP7 applies to synonymous (silent) variants predicted not to affect splicing. c.2194C>T is a missense variant (p.His732Tyr), not a synonymous variant. Details ▾Hide ▴

No further detail was recorded.

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.09). REVEL score = 0.338. BayesDel score = -0.0641334.

10 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.

Recorded publications

Mutational spectrum of the TSC1 gene in a cohort of 225 tuberous sclerosis complex patients: no evidence for genotype-phenotype correlation.

van Slegtenhorst M et al. · 1999

No paper-specific finding is recorded.

PMID 10227394 ↗
Hamartin variants that are frequent in focal dysplasias and cortical tubers have reduced tuberin binding and aberrant subcellular distribution in vitro.

Lugnier C et al. · 2009

No paper-specific finding is recorded.

PMID 19918125 ↗
Functional assessment of variants in the TSC1 and TSC2 genes identified in individuals with Tuberous Sclerosis Complex.

No paper-specific finding is recorded.

PMID 21309039 ↗
Lack of association of rare functional variants in TSC1/TSC2 genes with autism spectrum disorder.

No paper-specific finding is recorded.

PMID 23514105 ↗
A systematic approach to assessing the clinical significance of genetic variants.

No paper-specific finding is recorded.

PMID 24033266 ↗
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.

No paper-specific finding is recorded.

PMID 25741868 ↗
A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

No paper-specific finding is recorded.

PMID 26467025 ↗
Minute amounts of hamartin wildtype rescue the emergence of tuber-like lesions in conditional Tsc1 ablated mice.

Robens BK et al. · 2016

No paper-specific finding is recorded.

PMID 27425891 ↗
ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007.

No paper-specific finding is recorded.

PMID 18414213 ↗
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

No paper-specific finding is recorded.

PMID 28492532 ↗

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

gnomAD v4.1 5,806 / 1,612,416 recorded alleles Open source ↗

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

SpliceAI Lookup Recorded maximum delta 0.090 Open source ↗

ClinVar 23 Benign · 4 Likely 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= 0.002062975027144408, 38/18420 alleles, homozygotes = 0).

ClinVar

This variant has been reported in ClinVar as Benign (23 clinical laboratories) and as Likely benign (4 clinical laboratories). (ClinVarID = 5103)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.09). REVEL score = 0.338. BayesDel score = -0.0641334.

Functional

Somatic

This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV104404438, n = 6 times).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.