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_000314.7(PTEN):c.367C>G (p.His123Asp)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA377482278

428277 (ClinVar)

Gene: PTEN

Condition: PTEN hamartoma tumor syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 363d5223-feca-47e8-a3b8-115e05778f7f

Approved on: 2019-11-22

Published on: 2019-12-04

HGVS expressions

NM_000314.7:c.367C>G

NM_000314.7(PTEN):c.367C>G (p.His123Asp)

NC_000010.11:g.87933126C>G

CM000672.2:g.87933126C>G

NC_000010.10:g.89692883C>G

CM000672.1:g.89692883C>G

NC_000010.9:g.89682863C>G

NG_007466.2:g.74688C>G

NM_000314.5:c.367C>G

NM_000314.6:c.367C>G

NM_001304717.2:c.886C>G

NM_001304718.1:c.-384C>G

NM_001304717.5:c.886C>G

NM_001304718.2:c.-384C>G

ENST00000371953.7:c.367C>G

ENST00000498703.1:n.193C>G

ENST00000610634.1:c.265C>G

Pathogenic

PM1 PM2 PS3 PP2 PS4_Supporting

Evidence Links 2

Expert Panel

PTEN VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

PTEN VCEP

PTEN c.367C>G (p.His123Asp) 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: Phosphatase activity <50% of wild type OR RNA, mini-gene, or other assay shows impact on splicing. (PMID 29706350, 21828076) PM1: Located at a residue within a catalytic motif as defined by the ClinGen PTEN Expert Panel. PM2: Absent in large sequenced populations (PMID 27535533). 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. PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (internal laboratory contributor SCV000580072.3)

PM1

This amino acid position, 123, is in a catalytic motif.

PM2

Not present in gnomAD (coverage >90X).

PS3

Comprehensive in vivo functional analysis of human PTEN using a heterologous yeast reconstitution system. Phosphatase activity was fully inactive (Rodríguez-Escudero I et al2011).

High-throughput functional assay testing PTEN lipid phosphatase activity score of -4.345802175 so this variant had truncation-like function and was 'TRUE'. PubMed:29706350

Comprehensive in vivo functional analysis of human PTEN using a heterologous yeast reconstitution system. Phosphatase activity was fully inactive. PubMed:21828076

PP2

Missense

PS4_Supporting

Teenager with fundic gland polyps diagnosed as a child with hamartomatous features, multiple lipomas, Hashimoto thyroiditis, right thigh hamartoma, macrocephaly, penile freckling. Pediatric CC score of 11 (1 point) (Ambry Genetics).

Curation History

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