ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.2392T>C (p.Cys798Arg)

dbSNP: rs1554293839
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000662657 SCV000785344 uncertain significance Lynch syndrome 4 2017-07-07 criteria provided, single submitter clinical testing
Invitae RCV000800315 SCV000940022 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2023-04-24 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PMS2 protein function. ClinVar contains an entry for this variant (Variation ID: 548764). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. The frequency data for this variant in the population databases (gnomAD) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 798 of the PMS2 protein (p.Cys798Arg).
Ambry Genetics RCV002458176 SCV002737116 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-30 criteria provided, single submitter clinical testing The p.C798R variant (also known as c.2392T>C), located in coding exon 14 of the PMS2 gene, results from a T to C substitution at nucleotide position 2392. The cysteine at codon 798 is replaced by arginine, an amino acid with highly dissimilar properties. This alteration was identified in 1/136 Turkish colorectal cancer patients undergoing multigene panel testing for hereditary cancer risk (Erdem HB et al. Turk J Med Sci, 2020 06;50:1015-1021). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Myriad Genetics, Inc. RCV000662657 SCV004019744 uncertain significance Lynch syndrome 4 2023-04-03 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.

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