Submissions for variant NM_000314.8(PTEN):c.376G>A (p.Ala126Thr)

dbSNP: rs1554898129

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000526114	SCV000645575	likely pathogenic	PTEN hamartoma tumor syndrome	2024-11-11	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 126 of the PTEN protein (p.Ala126Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with PTEN-related conditions (PMID: 21659347). ClinVar contains an entry for this variant (Variation ID: 468683). Invitae Evidence Modeling incorporating data from in vitro experimental studies (internal data) indicates that this missense variant is expected to disrupt PTEN function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects PTEN function (PMID: 26504226). This variant disrupts the p.Ala126 amino acid residue in PTEN. Other variant(s) that disrupt this residue have been determined to be pathogenic (internal data). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV001092595	SCV001249158	likely pathogenic	not provided	2019-12-01	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV002509427	SCV002819186	likely pathogenic	Hereditary cancer-predisposing syndrome	2022-09-08	criteria provided, single submitter	clinical testing