ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.2177C>T (p.Pro726Leu)

gnomAD frequency: 0.00001  dbSNP: rs876658439
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000214603 SCV000273644 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-01 criteria provided, single submitter clinical testing The p.P726L variant (also known as c.2177C>T), located in coding exon 13 of the PMS2 gene, results from a C to T substitution at nucleotide position 2177. The proline at codon 726 is replaced by leucine, 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.
Invitae RCV000477071 SCV000551986 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2023-11-24 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 726 of the PMS2 protein (p.Pro726Leu). 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 variant has not been reported in the literature in individuals affected with PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 230192). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 RCV000214603 SCV002530269 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-21 criteria provided, single submitter curation

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