ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.386C>T (p.Ala129Val) (rs752284380)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000233053 SCV000285132 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-04-11 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 129 of the PMS2 protein (p.Ala129Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs752284380, ExAC 0.02%). This variant has not been reported in the literature in individuals with PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 237915). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Ambry Genetics RCV000566584 SCV000674257 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-08 criteria provided, single submitter clinical testing Insufficient evidence
Counsyl RCV000662749 SCV000785531 uncertain significance Hereditary nonpolyposis colorectal cancer type 4 2017-09-12 criteria provided, single submitter clinical testing
Color RCV000566584 SCV000906810 uncertain significance Hereditary cancer-predisposing syndrome 2020-03-03 criteria provided, single submitter clinical testing

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