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Variant: NM_000314.8(PTEN):c.830C>T (p.Thr277Ile)

CA000207

184277 (ClinVar)

Gene: PTEN
Condition: PTEN hamartoma tumor syndrome
Inheritance Mode: Autosomal dominant inheritance
UUID: a777d351-791d-4ae1-8feb-2a6403a3fe1f
Approved on: 2023-06-14
Published on: 2023-10-19

HGVS expressions

NM_000314.8:c.830C>T
NM_000314.8(PTEN):c.830C>T (p.Thr277Ile)
NC_000010.11:g.87960922C>T
CM000672.2:g.87960922C>T
NC_000010.10:g.89720679C>T
CM000672.1:g.89720679C>T
NC_000010.9:g.89710659C>T
NG_007466.2:g.102484C>T
ENST00000686459.1:c.*416C>T
ENST00000688158.1:c.*941C>T
ENST00000688308.1:c.830C>T
ENST00000688922.1:c.751C>T
ENST00000693560.1:c.1349C>T
ENST00000371953.8:c.830C>T
ENST00000371953.7:c.830C>T
ENST00000472832.2:c.257C>T
NM_000314.5:c.830C>T
NM_000314.6:c.830C>T
NM_001304717.2:c.1349C>T
NM_001304718.1:c.239C>T
NM_000314.7:c.830C>T
NM_001304717.5:c.1349C>T
NM_001304718.2:c.239C>T

Pathogenic

Met criteria codes 6
PS3_Moderate PM2_Supporting PM6_Strong PP3 PP2 PS4_Supporting

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 3.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
PTEN VCEP
NM_000314.8(PTEN):c.830C>T (p.Thr277Ile) variant 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 3.0.0). Please see a summary of the rules and criteria codes in the “PTEN ACMG Specifications Summary” document (assertion method column). PS6_S: Two probands with presumed de novo occurrence (maternity/paternity not confirmed) in a patient with the disease and no family history. (PMID:25549896 and internal laboratory contributor). PS3_M: Phosphatase activity ≤ -1.11 per Mighell et al. 2018, PMID: 29706350. 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=0.988) PM2_P: Absent in large sequenced populations OR present at extremely low (<0.00001, 0.001%) allele frequency in the gnomAD cohort. (PMID 27535533). PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (PMID: 25549896).
Met criteria codes
PS3_Moderate
Functionally deficient score of -2.03 (TRUE). in Mighell et al. 2018
PM2_Supporting
Absent in gnomAD
PM6_Strong
Two probands with presumed de novo occurrence (maternity/paternity not confirmed) in a patient with the disease and no family history. (PMID:25549896 and internal laboratory contributor).
PP3
in silico REVEL score of 0.988
PP2
missense constraint
PS4_Supporting
Proband(s) with phenotype specificity score of 1-1.5. (PMID:25549896, a peds score of 7)
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