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.287C>T (p.Pro96Leu)

CA377482110

449089 (ClinVar)

Gene: PTEN (HGNC:5728)

Condition: PTEN hamartoma tumor syndrome (MONDO:0017623)

Inheritance Mode: Autosomal dominant inheritance

UUID: 8f7f63bb-496b-4b77-8258-d706ccc91766

Approved on: 2024-04-05

Published on: 2024-04-10

HGVS expressions

NM_000314.8:c.287C>T

NM_000314.8(PTEN):c.287C>T (p.Pro96Leu)

NC_000010.11:g.87933046C>T

CM000672.2:g.87933046C>T

NC_000010.10:g.89692803C>T

CM000672.1:g.89692803C>T

NC_000010.9:g.89682783C>T

NG_007466.2:g.74608C>T

ENST00000700029.2:c.287C>T

ENST00000710265.1:c.287C>T

ENST00000472832.3:c.287C>T

ENST00000688158.2:n.1022C>T

ENST00000688922.2:c.*117C>T

ENST00000700021.1:c.242C>T

ENST00000700022.1:c.287C>T

ENST00000700029.1:c.121C>T

ENST00000706954.1:c.287C>T

ENST00000706955.1:c.*322C>T

ENST00000686459.1:c.287C>T

ENST00000688158.1:c.*398C>T

ENST00000688308.1:c.287C>T

ENST00000688922.1:c.208C>T

ENST00000693560.1:c.806C>T

ENST00000371953.8:c.287C>T

ENST00000371953.7:c.287C>T

ENST00000498703.1:n.113C>T

ENST00000610634.1:c.185C>T

NM_000314.5:c.287C>T

NM_000314.6:c.287C>T

NM_001304717.2:c.806C>T

NM_001304718.1:c.-464C>T

NM_000314.7:c.287C>T

NM_001304717.5:c.806C>T

NM_001304718.2:c.-464C>T

Likely Pathogenic

PM2_Supporting PS3_Moderate PP3 PP2 PM6

BS4 BS3 BS1 BS2 BP7 BP5 BP3 BP2 BP4 BP1 PS2 PS4 PS1 BA1 PP1 PP4 PM4 PM3 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 3.1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

PTEN VCEP

PTEN c.287C>T (p.Pro96Leu) 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). PS3_Moderate: Functional studies supportive of a damaging effect on the gene or gene product. Score of this variant = -2.48 (≤ -1.11) on a high throughput phosphatase assay (PMID 29706350). PM2_Supporting: Absent in large sequenced populations (PMID 27535533). PM6: Assumed de novo, but without confirmation of paternity and maternity in a patient with the disease and no family history (internal laboratory contributor SCV000616840.3). 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 =0.933).

PM2_Supporting

Absent in gnomAD

PS3_Moderate

Functional studies supportive of a damaging effect on the gene or gene product. Score of this variant = -2.13 (≤ -1.11) on a high throughput phosphatase assay (PMID:29706350). Matreyek et al., variant is in possibly low abundance class – 0.48164 Mighell et al., score is -2.479382146 (TRUE) which is truncation like since less than -2.13

PP3

REVEL score > 0.7 (score of this variant = 0.933)

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.

PM6

Assumed de novo, but without confirmation of paternity and maternity in a patient with the disease and no family history. (internal laboratory contributor: SCV000616840.3)

BS4