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.380G>A (p.Gly127Glu)

CA377482305

428225 (ClinVar)

Gene: PTEN (HGNC:5728)

Condition: PTEN hamartoma tumor syndrome (MONDO:0017623)

Inheritance Mode: Autosomal dominant inheritance

UUID: e6e5c29e-1f51-4e2a-b97a-72ee191e7c2b

Approved on: 2026-06-17

Published on: 2026-06-24

HGVS expressions

NM_000314.8:c.380G>A

NM_000314.8(PTEN):c.380G>A (p.Gly127Glu)

NC_000010.11:g.87933139G>A

CM000672.2:g.87933139G>A

NC_000010.10:g.89692896G>A

CM000672.1:g.89692896G>A

NC_000010.9:g.89682876G>A

NG_007466.2:g.74701G>A

ENST00000700029.2:c.380G>A

ENST00000710265.1:c.380G>A

ENST00000472832.3:c.380G>A

ENST00000688158.2:n.1115G>A

ENST00000688922.2:c.*210G>A

ENST00000700021.1:c.335G>A

ENST00000700022.1:c.380G>A

ENST00000700029.1:c.214G>A

ENST00000706954.1:c.380G>A

ENST00000706955.1:c.*415G>A

ENST00000686459.1:c.380G>A

ENST00000688158.1:c.*491G>A

ENST00000688308.1:c.380G>A

ENST00000688922.1:c.301G>A

ENST00000693560.1:c.899G>A

ENST00000371953.8:c.380G>A

ENST00000371953.7:c.380G>A

ENST00000498703.1:n.206G>A

ENST00000610634.1:c.278G>A

NM_000314.5:c.380G>A

NM_000314.6:c.380G>A

NM_001304717.2:c.899G>A

NM_001304718.1:c.-371G>A

NM_000314.7:c.380G>A

NM_001304717.5:c.899G>A

NM_001304718.2:c.-371G>A

Likely Pathogenic

PM2_Supporting PP3 PP2 PM1 PS3_Moderate PS4_Moderate

PP1

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.380G>A (p.Gly127Glu or NC_000010.10:g.89692896G>A) 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). PM1: Located at a residue within a catalytic motif as defined by the ClinGen PTEN Expert Panel. PS3_M: Functional studies supportive of a damaging effect on the gene or gene product. Score of this variant = -2.68 (≤ -1.11) on a high throughput phosphatase assay (PMID:29706350). PS4: Proband(s) with phenotype specificity score of 2-3.5. (PMID 40564777). 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 =0.954). PM2_P: Absent in large sequenced populations OR present at extremely low (<0.00001, 0.001%) allele frequency in the gnomAD cohort. (PMID 27535533).

PM2_Supporting

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

PP3

REVEL score > 0.7 (score of this variant =0.954)

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.

PS3_Moderate

Functional studies supportive of a damaging effect on the gene or gene product. Score of this variant = -2.68 (≤ -1.11) on a high throughput phosphatase assay (PMID:29706350).

PS4_Moderate

Proband(s) with phenotype specificity score of 2-3.5. (PMID 40564777). Proband #1: 15 yr old F born with postnatal macrosomia (4350 g/54 cm) and macrocephaly. Seen by cardiologist until the age 11 yrs due to interventricular septal defect,. Mixed germ cell tumor consisting of mature teratoma and yolk salk tumor on right ovary (age =7). Follicular adenoma on left lobe of thyroid gland (age =10). +5 Pediatric phenotype points, + 1 proband point. Proband #2: Younger brother of Proband #1. Macrosomia, macrocephaly, papillomatosis of the palatine tonsils, right-sided cryptochidism, aplasia of right testis, macular pigmentation of the penis. +9 Pediatric phenotype points, +1 proband point. Total proband points for Proband #1 and #2 = 1. Due to probands being related. Proband #3: Father of Proband #1 and #2, has macrocephaly and penile lentiginosis. CC score of +12, no weight added. (PMID 40564777) Ambry #1: 4yo male with CAL spots, macrocephaly, scoliosis, penile freckling, leg weakness, and hypertrichosis. +5 Pedistric phenotype score, +1 proband point.

PP1

PP1 requires co-segregation with disease in multiple affected family members, with 3 or 4 meioses, only two meiosis observed in PMID 40564777.

Curation History

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