Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000314.6(PTEN):c.331T>C (p.Trp111Arg)

Curation Version - 2.0
Curation History
JSON LD for Version 2.0

CA000401

92820 (ClinVar)

Gene: PTEN

Condition: PTEN hamartoma tumor syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 59486401-1daa-48dc-813f-bde6605d8cfd

Approved on: 2025-12-05

Published on: 2025-12-17

HGVS expressions

NM_000314.6:c.331T>C

NM_000314.6(PTEN):c.331T>C (p.Trp111Arg)

NC_000010.11:g.87933090T>C

CM000672.2:g.87933090T>C

NC_000010.10:g.89692847T>C

CM000672.1:g.89692847T>C

NC_000010.9:g.89682827T>C

NG_007466.2:g.74652T>C

ENST00000700029.2:c.331T>C

ENST00000710265.1:c.331T>C

ENST00000472832.3:c.331T>C

ENST00000688158.2:n.1066T>C

ENST00000688922.2:c.*161T>C

ENST00000700021.1:c.286T>C

ENST00000700022.1:c.331T>C

ENST00000700029.1:c.165T>C

ENST00000706954.1:c.331T>C

ENST00000706955.1:c.*366T>C

ENST00000686459.1:c.331T>C

ENST00000688158.1:c.*442T>C

ENST00000688308.1:c.331T>C

ENST00000688922.1:c.252T>C

ENST00000693560.1:c.850T>C

ENST00000371953.8:c.331T>C

ENST00000371953.7:c.331T>C

ENST00000498703.1:n.157T>C

ENST00000610634.1:c.229T>C

NM_000314.5:c.331T>C

NM_001304717.2:c.850T>C

NM_001304718.1:c.-420T>C

NM_000314.7:c.331T>C

NM_001304717.5:c.850T>C

NM_001304718.2:c.-420T>C

NM_000314.8:c.331T>C

Pathogenic

PS3_Moderate PM2 PS4_Moderate PM6_Strong PP2 PP3

PM5 PM3 PM1 PM4 PVS1 BA1 BS2 BS4 BS3 BS1 BP2 BP3 BP1 BP4 BP5 BP7 PS1 PS2 PP4 PP1

Evidence Links 0

Expert Panel

PTEN VCEP

Criteria Specification Information

Criteria Specification: ClinGen PTEN Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for PTEN Version 3.1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

PTEN VCEP

PTEN c.331T>C (p.Trp111Arg) meets criteria to be classified as pathogenic for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (PMID 30311380). Please see a summary of the rules and criteria codes in the “PTEN ACMG Specifications Summary” document (assertion method column). PS3_M: Functional studies showing a damaging effect on protein function. Phosphatase activity ≤ -1.11 per Mighell et al. 2018 (PMID: 29706350). This variant: score of -4.10 PM2_P: Absent in large sequenced populations (PMID 27535533). PS4_M: Probands with phenotype specificity score of 2-3.5. (internal laboratory contributor(s) ClinVar Organization ID: 61756, ClinVar Organization ID: 19864) PP2: PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease. PP3: REVEL score > 0.7 (score of this variant =0.961) PM6_S: Assumed de novo, but without confirmation of paternity and maternity in a patient with the disease and no family history and high phenotype specificity (PMID 35102303)

PS3_Moderate

Mighell = -4.1

PM2

Absent in gnomAD

PS4_Moderate

Internal lab submitters Ambry (Organization ID: 61756) case with 1 phenotype specificity point; Eng lab (Organization ID: 19864) case with 1 phenotype specificity point

PM6_Strong

Constitutional mosaicism in PMID 35102303, adult with CC score = 36. Parents not tested but VAF 29-34% and mosaic on Sanger. Criteria approved for use by the VCEP given constitutional mosaicism indicates variant arose during embryogenesis (de novo).

PP2