Variant: NM_000314.8(PTEN):c.113C>T (p.Pro38Leu)

Version: 1.0
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CA377784501

818421 (ClinVar)

Gene: PTEN (HGNC:5728)

Condition: PTEN hamartoma tumor syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: 9083923e-5318-4eca-a618-b119cb117c46

Approved on: 2023-10-11

Published on: 2023-10-18

HGVS expressions

NM_000314.8:c.113C>T
NM_000314.8(PTEN):c.113C>T (p.Pro38Leu)
NC_000010.11:g.87894058C>T
CM000672.2:g.87894058C>T
NC_000010.10:g.89653815C>T
CM000672.1:g.89653815C>T
NC_000010.9:g.89643795C>T
NG_007466.2:g.35620C>T
ENST00000686459.1:c.113C>T
ENST00000688158.1:c.*275+13620C>T
ENST00000688308.1:c.113C>T
ENST00000693560.1:c.632C>T
ENST00000371953.8:c.113C>T
ENST00000371953.7:c.113C>T
ENST00000462694.1:n.115C>T
ENST00000610634.1:c.11C>T
NM_000314.5:c.113C>T
NM_000314.6:c.113C>T
NM_001304717.2:c.632C>T
NM_001304718.1:c.-593C>T
NM_000314.7:c.113C>T
NM_001304717.5:c.632C>T
NM_001304718.2:c.-593C>T

Pathogenic

• Met criteria codes: PS4_Supporting PS2_Very Strong PP3 PP2 PS3_Moderate PM2_Supporting

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

Evidence submitted by expert panel

PTEN VCEP

NM_000314.8(PTEN):c.113C>T (p.Pro38Leu) meets criteria to be classified as 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). PS2_VS: Two proven de novo observations in a patient with the disease and no family history. (internal laboratory contributor: SCV002757182.1). PS3_M: Functional studies supportive of a damaging effect on the gene or gene product. Score of this variant = -3.772 (≤ -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: SCV002757182.1). PM2_P: Absent in gnomAD. 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 = 0.923)

Met criteria codes

• PS4_Supporting: Proband(s) with phenotype specificity score of 1-1.5. (internal laboratory contributor: SCV002757182.1)
• PS2_Very Strong: At least two proven OR one proven plus two assumed de novo observations in a patient with the disease and no family history. (internal laboratory contributor: SCV002757182.1)
• PP3: REVEL score of 0.923
• PP2: missense constraint
• PS3_Moderate: Lipid phosphatase activity score of -3.772374452 (TRUE) in Mighell et al. 2018 PMID: 29706350.
• PM2_Supporting: Absent in gnomAD