Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene label mismatch: PTEN vs undefined
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • Despite there being a valid 'cspec' property in the messages there's a discrepancy in message contents and CSPEC data: * Message Gene: PTEN CSPEC Genes: [ 'PTEN' ] * Message MONDOs: MONDO:0017623 CSPEC MONDO: []
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000314.8(PTEN):c.752G>T (p.Gly251Val)

CA377484997

536548 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 93b161cc-a3f6-4dd0-8b7b-3e0e31efe08a
Approved on: 2025-04-04
Published on: 2025-06-05

HGVS expressions

NM_000314.8:c.752G>T
NM_000314.8(PTEN):c.752G>T (p.Gly251Val)
NC_000010.11:g.87957970G>T
CM000672.2:g.87957970G>T
NC_000010.10:g.89717727G>T
CM000672.1:g.89717727G>T
NC_000010.9:g.89707707G>T
NG_007466.2:g.99532G>T
ENST00000700029.2:c.752G>T
ENST00000710265.1:c.752G>T
ENST00000472832.3:c.752G>T
ENST00000688158.2:n.1487G>T
ENST00000688922.2:c.*582G>T
ENST00000700021.1:c.707G>T
ENST00000700022.1:c.*91G>T
ENST00000700023.1:n.1910G>T
ENST00000700024.1:n.2144G>T
ENST00000700025.1:n.1521G>T
ENST00000700026.1:n.389G>T
ENST00000700029.1:c.586G>T
ENST00000706954.1:c.752G>T
ENST00000706955.1:c.*787G>T
ENST00000686459.1:c.*338G>T
ENST00000688158.1:c.*863G>T
ENST00000688308.1:c.752G>T
ENST00000688922.1:c.673G>T
ENST00000693560.1:c.1271G>T
ENST00000371953.8:c.752G>T
ENST00000371953.7:c.752G>T
ENST00000472832.2:c.179G>T
NM_000314.5:c.752G>T
NM_000314.6:c.752G>T
NM_001304717.2:c.1271G>T
NM_001304718.1:c.161G>T
NM_000314.7:c.752G>T
NM_001304717.5:c.1271G>T
NM_001304718.2:c.161G>T
More

Likely Pathogenic

Met criteria codes 6
PS2 PP1 PP3 PP2 PM2_Supporting PS4_Supporting
Not Met criteria codes 2
PS1 PS3

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen PTEN Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for PTEN Version 3.1.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
PTEN VCEP
PTEN c.752G>T (p.Gly251Val) meets criteria to be classified as likely 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 submitter ID 26957). PP3: REVEL score > 0.7 (score of this variant = 0.968). 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. PP1: Co-segregation with disease in multiple affected family members, with 3 or 4 meioses observed (internal laboratory contributor(s) SCV002669136.2). PS4_P: Proband(s) with phenotype specificity score of 1-1.5 (internal laboratory contributor(s) SCV002669136.2). PM2_P: Absent in large sequenced populations (PMID 27535533).
Met criteria codes
PS2
GeneDx: Confirmed de novo case in child (PED score = 4)
PP1
3 meioses. Segregates in family of Ambry proband (pos for variant) used for PS4: Mother in 20s neg w/ no clinical hx; Father in 20s pos (de novo) w/ large head, high BP, colonic polyps, esophageal ca; Brother pos w/ ASD, sig speech delay, large head; Brother pos w/ macrocephaly, dermal melanotyctosis, CAL (x1); GM in 40s neg w/ no clinical hx; Male relative (r/ship unknown) in 50s w/ no clinical hx.
PP3
REVEL score (0.968) > 0.7
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2_Supporting
Absent in gnomAD v2 and v4
PS4_Supporting
Ambry: M child w/ intussusception, large hamartoma, 10 total polyps, macrocephaly (PED score = 5)
Not Met criteria codes
PS1
c.752_753delinsTG (p.Gly251Val): Variant with limited evidence
PS3
Mighell et al 2018 (PMID 29706350): Low confidence result
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.