ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.371C>A (p.Thr124Asn)

dbSNP: rs1034709810
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001295818 SCV001484764 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2024-09-22 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 124 of the PMS2 protein (p.Thr124Asn). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 999781). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt PMS2 protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Sema4, Sema4 RCV002258185 SCV002530336 uncertain significance Hereditary cancer-predisposing syndrome 2021-05-30 criteria provided, single submitter curation
Ambry Genetics RCV002258185 SCV002620249 uncertain significance Hereditary cancer-predisposing syndrome 2020-07-21 criteria provided, single submitter clinical testing The p.T124N variant (also known as c.371C>A), located in coding exon 5 of the PMS2 gene, results from a C to A substitution at nucleotide position 371. The threonine at codon 124 is replaced by asparagine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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