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]

Link to SEPIO compliant JSON-LD document

Variant: NM_000314.7(PTEN):c.389G>C (p.Arg130Pro)

CA000439

142018 (ClinVar)

Gene: PTEN

Condition: PTEN hamartoma tumor syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 10bca2c6-405c-4f3a-919f-53db4e026879

Approved on: 2019-11-22

Published on: 2019-12-11

HGVS expressions

NM_000314.7:c.389G>C

NM_000314.7(PTEN):c.389G>C (p.Arg130Pro)

NC_000010.11:g.87933148G>C

CM000672.2:g.87933148G>C

NC_000010.10:g.89692905G>C

CM000672.1:g.89692905G>C

NC_000010.9:g.89682885G>C

NG_007466.2:g.74710G>C

NM_000314.5:c.389G>C

NM_000314.6:c.389G>C

NM_001304717.2:c.908G>C

NM_001304718.1:c.-362G>C

NM_001304717.5:c.908G>C

NM_001304718.2:c.-362G>C

ENST00000371953.7:c.389G>C

ENST00000498703.1:n.215G>C

ENST00000610634.1:c.287G>C

Pathogenic

PS3 PP2 PM1 PM2 PS4_Supporting

PS1 PS2 PP3 PP1 PM4 PM6 BA1 BS2 BS1 BS3 BS4 BP4 BP2 BP5 BP7

Evidence Links 1

Expert Panel

PTEN VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

PTEN VCEP

PTEN c.389G>C (p.Arg130Pro) 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 (PMID 29706350) 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 SCV000185699.6)

PS3

High-throughput functional assay testing PTEN Lipid Phosphatase Activity. R130P had a score of -3.153431338 and was 'true' indicating function was truncation-like for PS3.

High-throughput functional assay testing PTEN Lipid Phosphatase Activity. R130P had a score of -3.153431338 and was 'true' indicating function was truncation-like for PS3. PubMed:29706350

PP2

Missense.

PM1

Affects amino acid position 130, which is in a catalytic motif.

PM2

Not present in gnomAD (coverage >90X).

PS4_Supporting

Proband in 60s with goiter, thyroid ca in 20s, kidney cancer in 60s, ganglioneuroma, >10 colon polyps, macrocephaly. (1 point) (Ambry Genetics).

PS1