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_000314.8(PTEN):c.530A>G (p.Tyr177Cys)

CA377484342

580948 (ClinVar)

Gene: PTEN (HGNC:5728)

Condition: PTEN hamartoma tumor syndrome (MONDO:0017623)

Inheritance Mode: Autosomal dominant inheritance

UUID: d54df80d-a2f1-4e6b-88d4-e3884ce1c395

Approved on: 2025-12-05

Published on: 2025-12-17

HGVS expressions

NM_000314.8:c.530A>G

NM_000314.8(PTEN):c.530A>G (p.Tyr177Cys)

NC_000010.11:g.87952155A>G

CM000672.2:g.87952155A>G

NC_000010.10:g.89711912A>G

CM000672.1:g.89711912A>G

NC_000010.9:g.89701892A>G

NG_007466.2:g.93717A>G

ENST00000700029.2:c.530A>G

ENST00000710265.1:c.530A>G

ENST00000472832.3:c.530A>G

ENST00000688158.2:n.1265A>G

ENST00000688922.2:c.*360A>G

ENST00000700021.1:c.485A>G

ENST00000700022.1:c.493-5698A>G

ENST00000700023.1:n.1688A>G

ENST00000700024.1:n.1922A>G

ENST00000700025.1:n.1299A>G

ENST00000700029.1:c.364A>G

ENST00000706954.1:c.530A>G

ENST00000706955.1:c.*565A>G

ENST00000686459.1:c.*116A>G

ENST00000688158.1:c.*641A>G

ENST00000688308.1:c.530A>G

ENST00000688922.1:c.451A>G

ENST00000693560.1:c.1049A>G

ENST00000371953.8:c.530A>G

ENST00000371953.7:c.530A>G

NM_000314.5:c.530A>G

NM_000314.6:c.530A>G

NM_001304717.2:c.1049A>G

NM_001304718.1:c.-62A>G

NM_000314.7:c.530A>G

NM_001304717.5:c.1049A>G

NM_001304718.2:c.-62A>G

Likely Pathogenic

PM2_Supporting PP3 PS4 PS3_Moderate

Evidence Links 0

Expert Panel

PTEN VCEP

Criteria Specification Information

Criteria Specification: ClinGen PTEN Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for PTEN Version 3.1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

PTEN VCEP

PTEN c.530 (p.Tyr177Cys) meets criteria to be classified as likely pathogenic for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (ACMG Classification Rules Specified for PTEN Variant Curation version 3.1.0). Please see a summary of the rules and criteria codes in the “PTEN ACMG Specifications Summary” document (assertion method column). 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_M: Functional studies supportive of a damaging effect on the gene or gene product. Score of this variant = -2.19 (≤ -1.11) on a high throughput phosphatase assay (PMID:29706350). PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (internal laboratory contributor(s): SCV002643107.2, SCV005439375.1, SCV000833590.5) PM2_P: Absent in large sequenced populations

PM2_Supporting

Ultra-rare in population databases (allele frequency < 0.001%)

PP3

REVEL score > 0.7. The REVEL score is .97

PS4

Ambry 1 - male proband with sebaceous carcinoma, previous skin cancer (NOS) x2 in 30s. FHx: Mother with skin cancer NOS and history of 2-5 polyps; Father with prostate cancer in 60s and hx of 2-5 polyps. Sebaceous carcinoma is rare and highly specific for PHTS. Gene DX- Observed via exome (no parents tested though) in a kid with autism, seizures, dural AV fistules (counts as AVM), and macrocephaly. LabCorp We have observed this variant in approximately 5 individuals none of whom were counted as clinical evidence. Clinical indications for testing included epilepsy and macrocephaly, coarse facies, delays.

PS3_Moderate

study demonstrates impaired lipid phosphatase activity (PMID: 29706350 & 29785012);

Curation History

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