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.830C>G (p.Thr277Arg)

CA377485523

428268 (ClinVar)

Gene: PTEN

Condition: PTEN hamartoma tumor syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 579af9bf-2984-45d2-8e0a-bd0802a7860b

HGVS expressions

NM_000314.7:c.830C>G

NM_000314.7(PTEN):c.830C>G (p.Thr277Arg)

NC_000010.11:g.87960922C>G

CM000672.2:g.87960922C>G

NC_000010.10:g.89720679C>G

CM000672.1:g.89720679C>G

NC_000010.9:g.89710659C>G

NG_007466.2:g.102484C>G

NM_000314.5:c.830C>G

NM_000314.6:c.830C>G

NM_001304717.2:c.1349C>G

NM_001304718.1:c.239C>G

NM_001304717.5:c.1349C>G

NM_001304718.2:c.239C>G

NM_000314.8:c.830C>G

ENST00000371953.7:c.830C>G

ENST00000472832.2:n.257C>G

Likely Pathogenic

PS3 PP2 PM2 PP1_Moderate

BS2 BS1 BS3 BS4 PVS1 BP5 BP7 BP4 BP2 PS1 PS2 PS4 BA1 PP3 PM6 PM4 PM1 PM5

Evidence Links 2

Expert Panel

PTEN VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

PTEN VCEP

PTEN c.830C>G (p.Thr277Arg) meets criteria to be classified as likely 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) PM2: Absent in large sequenced populations PP1_M: Co-segregation with disease in multiple affected family members, with 5 or 6 meioses observed. (PMID 23335809) 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.

PS3

Mighell et al. 2018 High-throughput functional assay testing PTEN lipid phosphatase activity. T277R had a score of -3.839319668 and was 'TRUE', which means this variant had truncation-like function.

High-throughput functional assay testing PTEN lipid phosphatase activity. T277R had a score of -3.839319668 and was 'TRUE', which means this variant had truncation-like function. PubMed:29706350

PP2

Missense

PM2

Not present in gnomAD (coverage >30x).

PP1_Moderate

Pedigree provided by Dr. Longy confirming 5 meioses.

PubMed:23335809

BS2