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.278A>C (p.His93Pro)

CA377482091

468680 (ClinVar)

Gene: PTEN

Condition: PTEN hamartoma tumor syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 873374be-9923-42a8-9969-959167a621e8

HGVS expressions

NM_000314.8:c.278A>C

NM_000314.8(PTEN):c.278A>C (p.His93Pro)

NC_000010.11:g.87933037A>C

CM000672.2:g.87933037A>C

NC_000010.10:g.89692794A>C

CM000672.1:g.89692794A>C

NC_000010.9:g.89682774A>C

NG_007466.2:g.74599A>C

ENST00000700029.2:c.278A>C

ENST00000710265.1:c.278A>C

ENST00000472832.3:c.278A>C

ENST00000688158.2:n.1013A>C

ENST00000688922.2:c.*108A>C

ENST00000700021.1:c.233A>C

ENST00000700022.1:c.278A>C

ENST00000700029.1:c.112A>C

ENST00000706954.1:c.278A>C

ENST00000706955.1:c.*313A>C

ENST00000686459.1:c.278A>C

ENST00000688158.1:c.*389A>C

ENST00000688308.1:c.278A>C

ENST00000688922.1:c.199A>C

ENST00000693560.1:c.797A>C

ENST00000371953.8:c.278A>C

ENST00000371953.7:c.278A>C

ENST00000498703.1:n.104A>C

ENST00000610634.1:c.176A>C

NM_000314.5:c.278A>C

NM_000314.6:c.278A>C

NM_001304717.2:c.797A>C

NM_001304718.1:c.-473A>C

NM_000314.7:c.278A>C

NM_001304717.5:c.797A>C

NM_001304718.2:c.-473A>C

Likely Pathogenic

PP3 PP2 PM1 PM5 PM2_Supporting PS3_Moderate

Evidence Links 1

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

NM_000314.8(PTEN):c.278A>C (p.His93Pro) variant 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 3.0.0). Please see a summary of the rules and criteria codes in the “PTEN ACMG Specifications Summary” document (assertion method column). PS3_Moderate: Functional studies supportive of a damaging effect on the gene or gene product. Score of this variant = -3.95 (≤ -1.11) on a high throughput phosphatase assay (PMID:29706350). PM1: Located at a residue within a catalytic motif as defined by the ClinGen PTEN Expert Panel. PM5: Missense change at an amino acid residue where a different missense change determined to be pathogenic or likely pathogenic and with equal or lesser BLOSUM62 score has been seen before (ClinVar Variation ID 7848, SCV000886857.1). PM2_Supporting: 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 > 0.7 (score of this variant =0.974).

PP3

REVEL score > 0.7 (score of this variant=0.974)

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.

PM1

Located at a residue within a catalytic motif as defined by the ClinGen PTEN Expert Panel (this variant locates at WPD Loop, residues 90-94)

PM5

Missense change at an amino acid residue where a different missense change determined to be pathogenic or likely pathogenic and with equal or lesser BLOSUM62 score has been seen before (ClinVar Variation ID: 7848). - BLOSUM62 scoreof this variant) = -2 - BLOSUM62 score of PTEN c.278A>G p.His93Arg = 0 [VCEP classification = PATH]

PM2_Supporting

Absent in gnomAD

PS3_Moderate

Functional studies supportive of a damaging effect on the gene or gene product. Score of this variant = -3.95 (≤ -1.11) on a high throughput phosphatase assay (PMID:29706350).

Score = -3.95 (high_conf variant) PubMed:29706350

Approved on: 2024-02-09

Published on: 2024-03-04

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