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

  • See Evidence submitted by expert panel for details.

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

CA377482278

428277 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
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

Met criteria codes 5
PS3 PP2 PS4_Supporting PM1 PM2

Evidence Links 2

Expert Panel

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)
Met criteria codes
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).

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).
PM1
This amino acid position, 123, is in a catalytic motif.
PM2
Not present in gnomAD (coverage >90X).
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