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.131G>A (p.Gly44Asp)

CA377784538

427582 (ClinVar)

Gene: PTEN (HGNC:5728)

Condition: PTEN hamartoma tumor syndrome (MONDO:0017623)

Inheritance Mode: Autosomal dominant inheritance

UUID: 0cca48d0-e46c-4b58-b93d-f7a1f6a45afa

Approved on: 2026-05-06

Published on: 2026-06-08

HGVS expressions

NM_000314.8:c.131G>A

NM_000314.8(PTEN):c.131G>A (p.Gly44Asp)

NC_000010.11:g.87894076G>A

CM000672.2:g.87894076G>A

NC_000010.10:g.89653833G>A

CM000672.1:g.89653833G>A

NC_000010.9:g.89643813G>A

NG_007466.2:g.35638G>A

ENST00000700029.2:c.131G>A

ENST00000710265.1:c.131G>A

ENST00000472832.3:c.131G>A

ENST00000688158.2:n.899+13638G>A

ENST00000688922.2:c.131G>A

ENST00000700021.1:c.131G>A

ENST00000700022.1:c.131G>A

ENST00000706954.1:c.131G>A

ENST00000706955.1:c.*166G>A

ENST00000686459.1:c.131G>A

ENST00000688158.1:c.*275+13638G>A

ENST00000688308.1:c.131G>A

ENST00000693560.1:c.650G>A

ENST00000371953.8:c.131G>A

ENST00000371953.7:c.131G>A

ENST00000462694.1:n.133G>A

ENST00000610634.1:c.29G>A

NM_000314.5:c.131G>A

NM_000314.6:c.131G>A

NM_001304717.2:c.650G>A

NM_001304718.1:c.-575G>A

NM_000314.7:c.131G>A

NM_001304717.5:c.650G>A

NM_001304718.2:c.-575G>A

Pathogenic

PS2 PP3 PP2 PM6 PS4_Moderate PM2_Supporting PS3_Supporting

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 3.2.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

PTEN VCEP

PTEN c.131G>A (p.Gly44Asp) 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 3.1.0). 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. (PMID 28475857). PM6: Assumed de novo, but without confirmation of paternity and maternity in a patient with the disease and no family history. (internal laboratory contributor(s)). PS4_M: Probands with phenotype specificity score of 2-3.5. (PMID 19265751, 24375884, 28526761). 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 =0.96). PM2_ Supporting: Absent in large sequenced populations OR present at extremely low (<0.00001, 0.001%) allele frequency in the gnomAD cohort. (PMID 27535533). PS3_Supporting: Abnormal in vitro cellular assay or transgenic model with phenotype different from wild type that does not meet PS3. (PMID 21828076).

PS2

At least two proven OR one proven plus two assumed de novo observations in a patient with the disease and no family history. (PMID 28475857)

PP3

REVEL score > 0.7 (score of this variant =0.96)

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

One proband with presumed de novo occurrence (maternity/paternity not confirmed) for a patient with highly specific phenotype. (internal laboratory contributor(s))

PS4_Moderate

Case 1 (PMID: 19265751): Two year old female who presented with developmental delay, oral motor and speech delay, and macrocephaly (OFC of 54.5 cm (+5.0 S.D.)). History of bilateral hernia repair at one month of age, mild GE reflux, and benign macrocrania diagnosed at age 2 after having a normal CT scan. Large café au lait spot on her left lower chest and upper abdomen. +5 Pediatric phenotype score, +1 proband point Case 2 (PMID: 24375884): 10 m old M, macrocephaly (>> 2SD), mild motor delay, Physical exam: mild frontal bossing, MRI: Posterior periventricular multifocal white matter abnormalities, Enlarged perivascular spaces with CSF isointense signal. +6 pediatric phenotype points, +1 proband point. Case 3 (PMID: 28526761): Pediatric female patient presented with macrocephaly (+7SD), ASD, developmental delay, cafe au lait spot, and MRI finding of heterotopia. +7 pediatric phenptype points, +1 proband point.

PM2_Supporting

Absent in large sequenced populations OR present at extremely low (<0.00001, 0.001%) allele frequency in the gnomAD cohort. (PMID 27535533).

PS3_Supporting

Abnormal in vitro cellular assay or transgenic model with phenotype different from wild type that does not meet PS3. (PMID 21828076)

Curation History

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