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_000314.8(PTEN):c.182A>G (p.His61Arg)

CA000332

189402 (ClinVar)

Gene: PTEN

Condition: PTEN hamartoma tumor syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 33bda7f3-e4dc-4319-b832-5fc864c6bd1e

Approved on: 2023-12-01

Published on: 2023-12-14

HGVS expressions

NM_000314.8:c.182A>G

NM_000314.8(PTEN):c.182A>G (p.His61Arg)

NC_000010.11:g.87925530A>G

CM000672.2:g.87925530A>G

NC_000010.10:g.89685287A>G

CM000672.1:g.89685287A>G

NC_000010.9:g.89675267A>G

NG_007466.2:g.67092A>G

ENST00000686459.1:c.182A>G

ENST00000688158.1:c.*293A>G

ENST00000688308.1:c.182A>G

ENST00000688922.1:c.51A>G

ENST00000693560.1:c.701A>G

ENST00000371953.8:c.182A>G

ENST00000371953.7:c.182A>G

ENST00000498703.1:n.8A>G

ENST00000610634.1:c.80A>G

NM_000314.5:c.182A>G

NM_000314.6:c.182A>G

NM_001304717.2:c.701A>G

NM_001304718.1:c.-541-5516A>G

NM_000314.7:c.182A>G

NM_001304717.5:c.701A>G

NM_001304718.2:c.-541-5516A>G

Likely Pathogenic

PP3 PP2 PS4_Supporting PS3_Moderate PM2_Supporting

PP1 PM1 PM5

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 3.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

PTEN VCEP

PTEN c.182A>G (p.His61Arg) 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_M: Massively parallel functional assay interrogating phosphatase activity demonstrating a statistically significant difference from wild type (PMID: 29706350). PS4_P: Proband(s) with phenotype specificity score of 1-1.5 (PMID: 28526761). PM2_P: 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. PP3: REVEL score = 0.981.

PP3

REVEL score > 0.7 (score of this variant = 0.981)

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_Supporting

Hansen-Kiss (2017): 1 proband point for 17 yo M proband (see details below).

PS3_Moderate

Mighell 2018: high confidence variant, cum_score = -3.615

PM2_Supporting

Absent in gnomAD

PP1

1 Meiosis: Ambry #3: F in 50s w/ OFC 59.75 cm, thyroid adenoma @40s, breast ca @40s, 50s. Ambry #4 (son of Ambry #3): M in 30s w/ OFC 62 cm, ID.

PM1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM5

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

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