PTENc.203A>GUncertain significance

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Variant interpretation report

PTEN c.203A>G, p.(Tyr68Cys)

NM_000314.8:c.203A>G NP_000305.3:p.(Tyr68Cys) View identifiers

Classification

Uncertain significance

Variant description:

No variant summary was recorded for this case.

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

Uncertain.The recorded classification is uncertain significance.

In plain language

Gene-level background from the recorded interpretation.

About PTEN

No gene-level summary was recorded for this case.

Key facts

Condition: PTEN hamartoma tumor syndrome
Inheritance: Autosomal dominant
Evidence used: 1 moderate (pathogenic) · 3 supporting (pathogenic)
Expert rules: ClinGen PTEN VCEP v3.2
Other laboratories (ClinVar): 6 Pathogenic · 1 Likely pathogenic
Pipeline record: 22 Jul 2026 · version 7.0.4

Evidence considered

View criteria

Applied evidence criteria

PS3 (moderate): Y68C has a cumulative fitness score (Cum_score) of -2.73 in the Mighell et al. 2018 (PMID: 29706350) PTEN saturation mutagenesis phosphatase activity assay (Table S2), meeting the VCEP PS3_Moderate threshold of ≤ -1.11. The measurement is high-confidence (High_conf=True, Pass SE Filter). This represents systematic functional characterization of all possible missense variants at position 68 via massively parallel assay.
PM2 (supporting): NM_000314.8:c.203A>G is absent from gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada v1.0. This meets the PTEN VCEP PM2_Supporting threshold of allele frequency < 0.00001 (0.001%).
PP2 (supporting): PTEN is a gene with a low rate of benign missense variation (high missense constraint) and missense variants are a well-established common mechanism of disease in Cowden syndrome and related PTEN hamartoma tumor syndromes. NM_000314.8:c.203A>G is a missense variant meeting the PTEN VCEP PP2_Supporting criteria.
PP3 (supporting): REVEL score of 0.985 exceeds the PTEN VCEP PP3_Supporting threshold of >0.7 for missense variants. BayesDel score of 0.594 provides additional supporting computational evidence, though the VCEP rule specifies REVEL for missense variants.

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 ClinGen PTEN VCEP v3.2. 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: 4 Benign evidence criteria: 0

Pathogenic criteria applied · 4

PS3Moderate

PS3 · moderate

Y68C has a cumulative fitness score (Cum_score) of -2.73 in the Mighell et al. 2018 (PMID: 29706350) PTEN saturation mutagenesis phosphatase activity assay (Table S2), meeting the VCEP PS3_Moderate threshold of ≤ -1.11. The measurement is high-confidence (High_conf=True, Pass SE Filter). This represents systematic functional characterization of all possible missense variants at position 68 via massively parallel assay.

PM2Supporting

PM2 · supporting

NM_000314.8:c.203A>G is absent from gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada v1.0. This meets the PTEN VCEP PM2_Supporting threshold of allele frequency < 0.00001 (0.001%).

PP2Supporting

PP2 · supporting

PTEN is a gene with a low rate of benign missense variation (high missense constraint) and missense variants are a well-established common mechanism of disease in Cowden syndrome and related PTEN hamartoma tumor syndromes. NM_000314.8:c.203A>G is a missense variant meeting the PTEN VCEP PP2_Supporting criteria.

PP3Supporting

PP3 · supporting

REVEL score of 0.985 exceeds the PTEN VCEP PP3_Supporting threshold of >0.7 for missense variants. BayesDel score of 0.594 provides additional supporting computational evidence, though the VCEP rule specifies REVEL for missense variants.

Benign criteria applied · 0

No benign criterion marked as applied in the recorded assessment.

Recorded classification: Uncertain significance

ClinGen PTEN Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for PTEN Version 3.2 v3.2 criteria-combination framework was evaluated deterministically with applied criteria: PS3 moderate, PM2 supporting, PP2 supporting, PP3 supporting; no rule matched the adjudicated criteria.

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

Not recorded

gnomAD v4.1 allele counts were not recorded for this variant.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

Applied · PM2 →

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

SpliceAI score

0.010 maximum delta

Recorded SpliceAI maximum delta score: 0.010. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · PP3 → SpliceAI ↗

ClinVar submissions

7 reported laboratory submissions

6 Pathogenic · 1 Likely pathogenic. ClinVar API review status: criteria provided, multiple submitters, no conflicts.

Context only ClinVar ↗

Functional evidence

Statement recorded

OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.

Applied · PS3 → OncoKB ↗

COSMIC

Cancer Hotspots

Somatic evidence

9 recorded samples

This variant has previously been reported in somatic cancers (COSMIC; COSV64293993, n = 9 times).

Cancer Hotspots

This variant lies in a statistically significant hotspot.

Context only

COSMIC ↗Cancer Hotspots ↗

For specialists

Technical detail

ACMG/AMP criteria under ClinGen PTEN VCEP v3.2, with the data and sources behind each one.

29 criteria with recorded statuses: 4 met · 14 not met · 1 not assessed · 10 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic

PVS1 PS1 PS2 PS3 PS4 PM1 PM2 PM3 PM4 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

PS3_Moderate is met: Y68C has a cumulative fitness score of -2.73 in the Mighell et al. 2018 PTEN saturation mutagenesis phosphatase activity assay (Table S2 of PMID 29706350), meeting the PTEN VCEP threshold of ≤ -1.11 for PS3_Moderate.

PM2_Supporting is met: NM_000314.8:c.203A>G is absent from gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada v1.0, meeting the PTEN VCEP threshold of < 0.00001 (0.001%) allele frequency.

PP2_Supporting is met: PTEN has a low rate of benign missense variation and missense variants are a well-established common mechanism of disease in PTEN hamartoma tumor syndrome.

PP3_Supporting is met: REVEL score of 0.985 exceeds the PTEN VCEP threshold of > 0.7 for missense variants.

No benign criteria are met. The variant is absent from population databases, functional data demonstrates a damaging effect, and computational predictions support pathogenicity.

Classification: VUS (Variant of Uncertain Significance). The variant has 1 moderate criterion (PS3_Moderate) and 3 supporting criteria (PM2_Supporting, PP2_Supporting, PP3_Supporting). This combination (1M + 3Spt) does not meet any PTEN VCEP Likely Pathogenic rule (Rule13 requires ≥3M; Rule14 requires 2M + ≥2Spt; others require ≥1 Strong). Under both the PTEN VCEP and generic ACMG/AMP 2015 classification frameworks, this combination falls into the VUS category.

Met · 4

PS3 ModerateY68C has a cumulative fitness score (Cum_score) of -2.73 in the Mighell et al. 2018 (PMID: 29706350) PTEN saturation mutagenesis phosphatase activity assay (Table S2), meeting the VCEP PS3_Moderate threshold of ≤ -1.11. The measurement is high-confidence (High_conf=True, Pass SE Filter). This represents systematic functional characterization of all possible missense variants at position 68 via massively parallel assay. Details ▾Hide ▴

Evidence considered

Mighell et al. 2018 saturation mutagenesis: Y68C Cum_score = -2.73
High_conf=True
Pass SE Filter (≤ -1.11 threshold met for PS3_Moderate per PTEN VCEP)

Sources

vcep_mmc2

PM2 SupportingNM_000314.8:c.203A>G is absent from gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada v1.0. This meets the PTEN VCEP PM2_Supporting threshold of allele frequency < 0.00001 (0.001%). Details ▾Hide ▴

Evidence considered

Absent from gnomAD v2.1 (exomes)
Absent from gnomAD v4.1 (exomes)
Absent from gnomAD-Canada v1.0 (genomes)

Sources

gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗

PP2 SupportingPTEN is a gene with a low rate of benign missense variation (high missense constraint) and missense variants are a well-established common mechanism of disease in Cowden syndrome and related PTEN hamartoma tumor syndromes. NM_000314.8:c.203A>G is a missense variant meeting the PTEN VCEP PP2_Supporting criteria. Details ▾Hide ▴

Evidence considered

PTEN: high gnomAD missense constraint
missense variants are common disease mechanism in PHTS

Sources

cspec ↗

PP3 SupportingREVEL score of 0.985 exceeds the PTEN VCEP PP3_Supporting threshold of >0.7 for missense variants. BayesDel score of 0.594 provides additional supporting computational evidence, though the VCEP rule specifies REVEL for missense variants. Details ▾Hide ▴

Evidence considered

REVEL score: 0.985 (>0.7 VCEP threshold)
BayesDel score: 0.594 (additional support)

Sources

revelbayesdel

Not met · 14 · evaluated, threshold not reached

PS1 PS1 requires a different nucleotide change resulting in the same amino acid as a previously established pathogenic variant, or a variant at the same nucleotide position as a known pathogenic splicing variant. c.203A>G is the only nucleotide change that produces p.Tyr68Cys (TAC→TGC), and the variant is a missense, not a splicing variant. Details ▾Hide ▴

No further detail was recorded.

PS2 No de novo observation identified in the reviewed literature. The only case report with detailed pedigree (PMID: 26246517) describes an inherited variant — the proband's father also carries c.203A>G and has macrocephaly. No confirmed or assumed de novo evidence exists for this variant. Details ▾Hide ▴

Evidence considered

PMID 26246517: variant inherited from father
not de novo

PM1 The PTEN VCEP defines PM1 as applicable to residues in the catalytic motifs: 90-94, 123-130, and 166-168 (NP_000305.3). p.Tyr68Cys is at position 68, which lies within the ATP-binding motif (residues 60-73) but outside the VCEP-specified catalytic motif ranges. Although residue 68 is in a statistically significant cancer hotspot per cancerhotspots.org, the VCEP definition explicitly limits PM1 to the named catalytic residues. Details ▾Hide ▴

Evidence considered

Y68 is in ATP-binding Type-B motif (residues 60-73 per PMID 19457929)
but outside VCEP-defined catalytic motifs (90-94
123-130
166-168)

Sources

cspec ↗

PM5 PM5 requires a different missense change at the same amino acid residue previously determined to be pathogenic or likely pathogenic. At codon 68, p.Tyr68Asp (Y68D, PMID: 16704655) and p.Tyr68His (Y68H, PMID: 9600246) have been reported, but neither has been confirmed with P/LP classification in ClinVar through the available data. Additionally, BLOSUM62 comparison could not be performed. Without verified P/LP comparator at the same residue, PM5 cannot be applied. Details ▾Hide ▴

Evidence considered

PMID 16704655: reports p.Y68D in Proteus syndrome (not our variant)
PMID 9600246: reports p.Y68H (c.202T>C
not c.203A>G) in CS
No P/LP classified different missense at codon 68 confirmed in collected data

Still missing

ClinVar classification for Y68D and Y68H not verified
if either is P/LP
PM5 may apply

PM6 No de novo observation identified. The one case with parental data (PMID: 26246517) shows inheritance from the father. Details ▾Hide ▴

Evidence considered

PMID 26246517: variant inherited
not de novo

PP1 Insufficient segregation data. PMID 26246517 reports one affected parent-child pair (father with macrocephaly), providing at most 1 meiosis. The PTEN VCEP requires ≥3 meioses for PP1_Supporting, ≥5 for Moderate, and ≥7 across ≥2 families for Strong. Details ▾Hide ▴

Evidence considered

PMID 26246517: proband and father share variant and macrocephaly (1 meiosis)

Still missing

Additional family segregation data would be needed to reach ≥3 meioses

BA1 The variant is absent from all gnomAD populations. The PTEN VCEP BA1 threshold is filtering allele frequency > 0.00056 (0.056%). Zero allele count does not meet this threshold. Details ▾Hide ▴

Evidence considered

Absent from gnomAD v2.1 and v4.1

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS1 The variant is absent from gnomAD. The PTEN VCEP BS1 threshold is allele frequency ≥ 0.000043 (0.0043%) for strong and ≥ 0.0000043 (0.00043%) for supporting. Zero allele count does not meet either threshold. Details ▾Hide ▴

Evidence considered

Absent from gnomAD v2.1 and v4.1

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS2 No homozygous observations of c.203A>G in any population database or published report. The PTEN VCEP BS2 requires observation in the homozygous state in a healthy or PHTS-unaffected individual. Details ▾Hide ▴

Evidence considered

No homozygous calls in gnomAD or literature

BS3 Functional data from Mighell et al. 2018 saturation mutagenesis (mmc2.xlsx) shows Y68C has a damaging effect on phosphatase activity (Cum_score = -2.73). The PTEN VCEP BS3 requires functional studies showing no damaging effect. The available evidence demonstrates the opposite — a deleterious functional consequence. Details ▾Hide ▴

Evidence considered

Mighell et al. 2018: Y68C Cum_score = -2.73 (damaging
not benign)

Sources

vcep_mmc2

BS4 No segregation data demonstrating lack of segregation in affected family members. PMID 26246517 shows co-occurrence of variant and phenotype (macrocephaly) in both proband and father, which is consistent with segregation, not lack thereof. Details ▾Hide ▴

Still missing

No families studied for lack of segregation

BP2 No evidence of the variant observed in trans with a pathogenic or likely pathogenic PTEN variant, nor ≥3 observations in cis/phase unknown with different P/LP PTEN variants. Details ▾Hide ▴

Still missing

No phase data available

BP4 The PTEN VCEP BP4 rule for missense variants requires REVEL score < 0.5. The REVEL score for c.203A>G is 0.985, strongly predicting a deleterious effect rather than no impact. SpliceAI shows no splicing impact (max delta = 0.01), but the REVEL criterion for missense variants is not met. Details ▾Hide ▴

Evidence considered

REVEL = 0.985 (does not meet <0.5 threshold)
SpliceAI max delta = 0.01 (no splicing impact
but BP4 missense rule uses REVEL)

Sources

revelspliceai ↗

BP5 No evidence that this variant has been found in a case with an alternate molecular basis for disease meeting the PTEN VCEP BP5 criteria (other gene/disorder must be highly penetrant, and the patient's personal/family history must show no overlap between the other gene disorder and PTEN). Details ▾Hide ▴

No further detail was recorded.

Not assessed · 1 · no assessment recorded

PS4 Insufficient proband-level data with specificity scores to apply PS4 per PTEN VCEP rules. The variant is reported in ClinVar as Pathogenic by 6 clinical laboratories and Likely Pathogenic by 1, and has been observed in CS patients (PMID: 19457929, PMID: 26246517), but individual proband specificity scores required by the VCEP PS4 framework (≥16 for Very Strong, 4-15.5 for Strong, 2-3.5 for Moderate, 1-1.5 for Supporting) could not be computed from available data. Details ▾Hide ▴

Evidence considered

ClinVar VCV000233777: 7 submissions (6 P
1 LP)
no expert panel review
PMID 19457929: identifies Y68C among ~400 CS patients screened
PMID 26246517: one proband with CS and immunodeficiency

Still missing

Proband specificity scores not available for PS4 scoring

Not applicable · 10· recorded as not applicable Show reasons ▾Hide reasons ▴

PVS1 N/ANM_000314.8:c.203A>G is a missense variant (p.Tyr68Cys). The PTEN VCEP PVS1 decision tree applies only to null variants (nonsense, frameshift, canonical ±1,2 splice site disruptions, and exon-level CNVs). Missense substitutions are outside the scope of PVS1. Details ▾Hide ▴

No further detail was recorded.

PM3 VCEPPM3 applies to recessive disorders where the variant is detected in trans with a pathogenic variant. PTEN-associated disorders are autosomal dominant, and PM3 is designated Not Applicable by the PTEN VCEP. Details ▾Hide ▴

No further detail was recorded.

PM4 N/APM4 applies to in-frame deletions/insertions in non-repeat regions or stop-loss variants. NM_000314.8:c.203A>G is a single-nucleotide missense substitution, not an in-frame indel or stop-loss variant. Details ▾Hide ▴

No further detail was recorded.

PP4 VCEPPP4 is designated as Not Applicable by the PTEN VCEP. Phenotype specificity has been incorporated into the PS4 rule specifications instead. Details ▾Hide ▴

No further detail was recorded.

PP5 VCEPPP5 is designated as Not Applicable by the PTEN VCEP. ClinVar review status is 'criteria provided, single submitter' (not 3-star expert panel), so even the PP5 override policy would not apply. Details ▾Hide ▴

No further detail was recorded.

BP1 VCEPBP1 is designated as Not Applicable by the PTEN VCEP. Details ▾Hide ▴

No further detail was recorded.

BP3 VCEPBP3 applies to in-frame deletions/insertions in repetitive regions without a known function. NM_000314.8:c.203A>G is a missense substitution, not an in-frame indel. Details ▾Hide ▴

No further detail was recorded.

BP6 VCEPBP6 is designated as Not Applicable by the PTEN VCEP. Details ▾Hide ▴

No further detail was recorded.

BP7 N/ABP7 applies to synonymous (silent) or intronic variants at or beyond +7/-21 with no predicted splice impact. NM_000314.8:c.203A>G is a missense variant (p.Tyr68Cys) and does not meet the variant type criteria for BP7. Details ▾Hide ▴

No further detail was recorded.

PS5 N/APS5 is not defined in the PTEN VCEP criteria set (ClinGen PTEN Expert Panel Specifications Version 3.2). Details ▾Hide ▴

No further detail was recorded.

Identifiers

Gene: PTEN
Transcript: NM_000314.8
Coding (HGVS c.): NM_000314.8:c.203A>G
Protein (HGVS p.): NP_000305.3:p.(Tyr68Cys)
GRCh38: chr10:87925551 A>G
GRCh37: chr10:89685308 A>G
ClinVar: 233777
COSMIC: COSV64293993

Gene diagram

Every interpreted variant in PTEN, mapped onto the exon structure of NM_000314.8. Select a row to find it on the plot.

PTENNM_000314.8

Fetching transcript structure from UCSC…

Exons

—

Transcript span

—

Strand

—

Variants mapped

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Source

UCSC ncbiRefSeqCurated

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

	Protein	Location	Classification	Link

gnomAD v4.1 Allele count data not recorded

gnomAD v2.1 Allele count data not recorded

gnomAD-Canada v1.0 Allele count data not recorded

Statements

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

SpliceAI and Pangolin

SpliceAI acceptor lossat -22 bp

0.000

SpliceAI acceptor gainat -38 bp

0.010

SpliceAI donor lossat -3 bp

0.000

SpliceAI donor gainat +10 bp

0.000

Pangolin splice lossmagnitude shown

-0.000

Pangolin splice gain

0.000

Other predictors

REVEL: 0.985
BayesDel: 0.594

How the predictions were used

Evidence considered

REVEL score: 0.985 (>0.7 VCEP threshold)
BayesDel score: 0.594 (additional support)

Sources

revelbayesdel

Evidence considered

REVEL = 0.985 (does not meet <0.5 threshold)
SpliceAI max delta = 0.01 (no splicing impact
but BP4 missense rule uses REVEL)

Sources

revelspliceai ↗

No further detail was recorded.

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.985. BayesDel score = 0.59441.

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

Recorded publications

Germline and somatic cancer-associated mutations in the ATP-binding motifs of PTEN influence its subcellular localization and tumor suppressive function.

Lobo GP et al. · 2009

Lobo et al. (2009) identified PTEN Y68C as a germline missense mutation in a Cowden syndrome patient. The variant lies within the Type-B ATP-binding motif (residues 60-73) of the phosphatase domain. Patient-derived lymphoblastoid cells showed increased nuclear PTEN protein compared to controls, suggesting altered subcellular localization. This was one of two germline mutations found in the Type-B ATP-binding site (Y68H and Y68C) among ~400 CS patients screened.
Names this variant
PMID 19457929 ↗
Quoted passage
Two patients had germline mutations in the B-Type ATP-binding site: Y68H and Y68C. Each of these mutations are novel missense mutations, which are highly predicted to be deleterious, although this has not been confirmed functionally.
Results: 'Germline PTEN mutations located in the ATP-binding domains identified in CS patients'; Figure 3B; Figure 5
Naturally occurring germline and tumor-associated mutations within the ATP-binding motifs of PTEN lead to oxidative damage of DNA associated with decreased nuclear p53.

He X et al. · 2011

He et al. (2011) studied functional consequences of PTEN ATP-binding motif mutations (K62R, Y65C, K125E) in breast carcinogenesis, focusing on p53 regulation, oxidative stress, and DNA damage. The paper mentions Y68H as a germline mutation in a CS patient used for lymphoblastoid protein expression analysis, but NM_000314.8:c.203A>G (Y68C) was not studied or mentioned.
Does not name this variant
PMID 20926450 ↗
Quoted passage
In contrast to PTEN, both cancer-associated somatic (WT PTEN, K62R PTEN and Y65C PTEN) and germline K125E PTEN missense mutations (PTEN and R130G PTEN), which lie within the ATP-binding motifs, result in nuclear mislocalization as a cellular phenotypic hallmark (Y68H)
Introduction: mentions Y68H; Materials and Methods: patient lymphoblastoid lines (Y68H and R130G only)
KLLN epigenotype-phenotype associations in Cowden syndrome.

Nizialek EA et al. · 2015

Nizialek et al. (2015) examined KLLN promoter methylation in Cowden syndrome patients and its associations with clinical phenotypes. The study focuses on KLLN epigenotype-phenotype correlations in PTEN mutation-negative CS/CSL patients. NM_000314.8:c.203A>G (Y68C) was not mentioned.
Does not name this variant
PMID 25669429 ↗
Cowden's syndrome with immunodeficiency.

Browning MJ et al. · 2015

Browning et al. (2015) report a 5-year-old boy with Cowden syndrome, macrocephaly, and panhypogammaglobulinemia who carries a heterozygous PTEN c.203A>G (p.Tyr68Cys) mutation. The variant was inherited from his father, who also has macrocephaly. Immunological workup revealed reduced PTEN protein expression and increased AKT and S6 phosphorylation in the proband's T cells.
Names this variant
PMID 26246517 ↗
Quoted passage
Genetic testing confirmed the presence of a heterozygous mutation in the PTEN gene (c.203A>G). This mutation, in a highly conserved area in exon 3, encodes an amino acid substitution from tyrosine to cysteine (p.Tyr68Cys) within the phosphatase domain.
Case Reports, Case 1; Figure 1A
The genetic basis of Cowden's syndrome: three novel mutations in PTEN/MMAC1/TEP1.

Tsou et al. (1998) report three novel germline PTEN mutations in Cowden syndrome: L112P (c.335T>C), a splice site mutation (801+2T>G), and Y68H (c.202T>C, TAC→CAC). The Y68H variant is a different nucleotide change at the same codon, not NM_000314.8:c.203A>G (Y68C, TAC→TGC).
Does not name this variant
PMID 9600246 ↗
Quoted passage
The third mutation we report is a missense mutation, consisting of a transition (T→C) at nucleotide 202 in exon 3, resulting in a tyrosine to histidine (TAC to CAC) change at codon 68.
Abstract; Results: Individual MHSF041-01 description
Epidermal naevus in Proteus syndrome showing loss of heterozygosity for an inherited PTEN mutation.

Loffeld A et al. · 2006

Loffeld et al. (2006) report a 3-year-old boy with Proteus syndrome and a novel germline p.Y68D mutation in PTEN inherited from his mother with Cowden syndrome. The epidermal naevus showed loss of heterozygosity for this mutation. The reported variant is Y68D (GAT), not Y68C (TGT).
Does not name this variant
PMID 16704655 ↗
Quoted passage
A 3-year-old boy with Proteus syndrome has a novel germline p.Y68D mutation of the PTEN gene inherited from his mother who has Cowden syndrome.
American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography.

Saslow et al. (2007) present American Cancer Society guidelines for breast MRI screening. This is a clinical practice guideline document that does not discuss specific PTEN variants.
Does not name this variant
PMID 17392385 ↗
PTEN Hamartoma Tumor Syndrome.

GeneReviews entry on PTEN Hamartoma Tumor Syndrome (Pilarski, 2019). Provides gene-level overview of PTEN-associated conditions but does not specifically discuss NM_000314.8:c.203A>G.
Does not name this variant
PMID 20301661 ↗

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

gnomAD v4.1 Captured gnomAD v4.1 source record Open source ↗

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

SpliceAI Lookup Recorded maximum delta 0.010 Open source ↗

ClinVar 6 Pathogenic · 1 Likely pathogenic 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 ↗

ClinGen CSpec Captured ClinGen CSpec 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

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

ClinVar

This variant has been reported in ClinVar as Pathogenic (6 clinical laboratories) and as Likely pathogenic (1 clinical laboratory). (ClinVarID = 233777)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01). REVEL score = 0.985. BayesDel score = 0.59441.

Functional

OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.

Somatic

This variant lies in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV64293993, n = 9 times).

Cancer Hotspots

This variant lies in a statistically significant hotspot.