Variant: NM_000314.7(PTEN):c.633C>G (p.Cys211Trp)

CA10603125

279878 (ClinVar)

Gene: PTEN

Condition: PTEN hamartoma tumor syndrome

Inheritance Mode: Autosomal dominant inheritance

UUID: d2e370c6-311c-4c89-a383-c956681b1dfc

Approved on: 2025-10-03

Published on: 2025-10-27

HGVS expressions

NM_000314.7:c.633C>G
NM_000314.7(PTEN):c.633C>G (p.Cys211Trp)
NC_000010.11:g.87952258C>G
CM000672.2:g.87952258C>G
NC_000010.10:g.89712015C>G
CM000672.1:g.89712015C>G
NC_000010.9:g.89701995C>G
NG_007466.2:g.93820C>G
ENST00000700029.2:c.633C>G
ENST00000710265.1:c.633C>G
ENST00000472832.3:c.633C>G
ENST00000688158.2:n.1368C>G
ENST00000688922.2:c.*463C>G
ENST00000700021.1:c.588C>G
ENST00000700022.1:c.493-5595C>G
ENST00000700023.1:n.1791C>G
ENST00000700024.1:n.2025C>G
ENST00000700025.1:n.1402C>G
ENST00000700029.1:c.467C>G
ENST00000706954.1:c.633C>G
ENST00000706955.1:c.*668C>G
ENST00000686459.1:c.*219C>G
ENST00000688158.1:c.*744C>G
ENST00000688308.1:c.633C>G
ENST00000688922.1:c.554C>G
ENST00000693560.1:c.1152C>G
ENST00000371953.8:c.633C>G
ENST00000371953.7:c.633C>G
ENST00000472832.2:c.60C>G
NM_000314.5:c.633C>G
NM_000314.6:c.633C>G
NM_001304717.2:c.1152C>G
NM_001304718.1:c.42C>G
NM_001304717.5:c.1152C>G
NM_001304718.2:c.42C>G
NM_000314.8:c.633C>G

Pathogenic

• Met criteria codes: PP3 PP2 PS2_Very Strong PM2_Supporting PS4_Moderate

• Not Met criteria codes: PS3 PM1 PM6

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

Evidence submitted by expert panel

PTEN VCEP

PTEN c.633C>G (p.Cys211Trp) 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_VS: Three pediatric patients (Internal lab contribution) confirmed de novo with WES trio. PP3: REVEL score >.7 (Score: 0.856). PS4_P: Vanderver et al (PMID 24375884) patient #21 with macrocephaly, developmental delay, and enlarged periventricular spaces. Phenotype score of +6, +1 proband point. Confirmed de novo pediatric patient with extreme macrocephaly (+4 SD), developmental delay, hemihypertrophy, autism and ID (Internal laboratory contribution). Phenotype score +5, +1 proband point. PM2_P: Absent in large sequenced populations (gnomad v4). 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.

Met criteria codes

• PP3: REVEL score >.7 (Score: 0.856).
• PP2: PTEN gene has a low rate of benign missense variation and where missense variants are a common mechanism of disease.
• PS2_Very Strong: Three pediatric patients (Internal lab contribution) confirmed de novo with WES trio.
• PM2_Supporting: Absent from gnomAD
• PS4_Moderate: Vanderver et al (PMID 24375884) patient #21 with macrocephaly, developmental delay, and enlarged periventricular spaces. Phenotype score of +6, +1 proband point. Confirmed de novo pediatric patient with extreme macrocephaly (+4 SD), developmental delay, hemihypertrophy, autism and ID (Internal laboratory contribution)

Not Met criteria codes

• PS3: Cumulative functional score of -1.002 in Miguell et al. 2018 (PMID: 29706350), indicating WT-like phosphatase activity.
• PM1: not in critical domain
• PM6: Internal lab contribution: one patient assumend de novo with macrocephaly and congenital heart defects. Pediatric phenotype score not high enough to receive weight.