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.1034T>C (p.Leu345Pro)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA377487108

484605 (ClinVar)

Gene: PTEN

Condition: PTEN hamartoma tumor syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 82136d77-950f-4f10-ad15-b80bd870a8ba

Approved on: 2021-06-04

Published on: 2022-09-30

HGVS expressions

NM_000314.8:c.1034T>C

NM_000314.8(PTEN):c.1034T>C (p.Leu345Pro)

NC_000010.11:g.87965294T>C

CM000672.2:g.87965294T>C

NC_000010.10:g.89725051T>C

CM000672.1:g.89725051T>C

NC_000010.9:g.89715031T>C

NG_007466.2:g.106856T>C

ENST00000686459.1:c.*620T>C

ENST00000688158.1:c.*1145T>C

ENST00000688308.1:c.1034T>C

ENST00000688922.1:n.955T>C

ENST00000693560.1:c.1553T>C

ENST00000371953.8:c.1034T>C

ENST00000371953.7:c.1034T>C

NM_000314.5:c.1034T>C

NM_000314.6:c.1034T>C

NM_001304717.2:c.1553T>C

NM_001304718.1:c.443T>C

NM_000314.7:c.1034T>C

NM_001304717.5:c.1553T>C

NM_001304718.2:c.443T>C

Pathogenic

PM2 PS4_Moderate PS2 PS3_Supporting PP2

Evidence Links 0

Expert Panel

PTEN VCEP

Criteria Specification Information

Criteria Specification: ClinGen PTEN Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 2

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

PTEN VCEP

PTEN c.1034T>C (p.Leu345Pro) meets criteria to be classified as 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). PS2: De novo (both maternity and paternity confirmed) observation in a patient with the disease and no family history. (internal laboratory contributor(s) ClinVar Organization ID: 26957) PM2: Absent in large sequenced populations (PMID 27535533). PS4_M: Probands with phenotype specificity score of 2-3.5. (PMID 21659347, internal laboratory contributor(s) ClinVar Organization ID: 26957) 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_P: Abnormal in vitro cellular assay or transgenic model with phenotype different from wild type that does not meet PS3. (PMID 29785012, PMID 29706350)

PM2

ABSENT

PS4_Moderate

1 point for internal GeneDx case, F child with macrocephaly, developmental delay, vascular malformation. Also 1 point for PMID 21659347 per VCEP discussion.

PS2

GeneDx case

PS3_Supporting

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

PP2

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

Curation History

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