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.1A>G (p.Met1Val)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA377781751

484600 (ClinVar)

Gene: PTEN

Condition: PTEN hamartoma tumor syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: b5f8e9e7-3f37-42d6-9844-c91a9757b411

Approved on: 2019-11-22

Published on: 2019-12-11

HGVS expressions

NM_000314.7:c.1A>G

NM_000314.7(PTEN):c.1A>G (p.Met1Val)

NC_000010.11:g.87864470A>G

CM000672.2:g.87864470A>G

NC_000010.10:g.89624227A>G

CM000672.1:g.89624227A>G

NC_000010.9:g.89614207A>G

NG_007466.2:g.6032A>G

NG_033079.1:g.3968T>C

NM_000314.5:c.1A>G

NM_000314.6:c.1A>G

NM_001304717.2:c.520A>G

NM_001304718.1:c.-705A>G

NM_001304717.5:c.520A>G

NM_001304718.2:c.-705A>G

ENST00000371953.7:c.1A>G

ENST00000462694.1:n.3A>G

ENST00000487939.1:n.22A>G

ENST00000610634.1:c.-102A>G

Pathogenic

PM2 PM6 PVS1 PS4_Moderate

PP2 PP3 PP1 PM4 PM1 PM5 BA1 BS2 BS1 BS3 BS4 BP5 BP7 BP4 BP2 PS2 PS3 PS1

Evidence Links 1

Expert Panel

PTEN VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

PTEN VCEP

PTEN c.1A>G (p.M1?) 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). PVS1: Null variant predicted to result in nonsense-mediated decay or causing truncation/frameshift at or 5’ to c.1121 (NM_000314.4). PM2: Absent in large sequenced populations (PMID 27535533). PM6: Assumed de novo, but without confirmation of paternity and maternity in a patient with the disease and no family history. (PMID 29752200) PS4_M: Probands with phenotype specificity score of 2-3.5. (PMID 29752200, 28774669; internal laboratory contributor ClinVar Organization ID: 26957)

PM2

Not present in gnomAD, coverage >90X.

PM6

Identified in a M Japanese patient (patient 6) as de novo, HC 60 @ 5yrs (+6 SD), sever DD, autism, distinctive facial features. Parents were healthy, but father had Graves' disease. They did not mention how the alteration was confirmed as de novo. CC score of 5 (Kato 2018 PubMed: 29752200)

PubMed:29752200

PVS1