ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1849C>T (p.Pro617Ser)

dbSNP: rs864622096
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000204145 SCV000259323 likely benign Hereditary nonpolyposis colorectal neoplasms 2023-11-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV001013406 SCV001173986 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-14 criteria provided, single submitter clinical testing The p.P617S variant (also known as c.1849C>T), located in coding exon 11 of the PMS2 gene, results from a C to T substitution at nucleotide position 1849. The proline at codon 617 is replaced by serine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV001775669 SCV002013074 uncertain significance not provided 2019-10-07 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Color Diagnostics, LLC DBA Color Health RCV001013406 SCV002051886 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-16 criteria provided, single submitter clinical testing This missense variant replaces proline with serine at codon 617 of the PMS2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. In a large breast cancer case-control study, this variant has been observed in 2/60466 cases and 4/53461 unaffected controls (PMID: 33471991). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Baylor Genetics RCV003462361 SCV004207840 uncertain significance Lynch syndrome 4 2023-05-14 criteria provided, single submitter clinical testing

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