ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1784T>C (p.Val595Ala)

dbSNP: rs1554297236
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000583738 SCV000691044 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces valine with alanine at codon 595 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. This variant has not been reported in individuals affected with PMS2-related disorders in the literature. 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.
Invitae RCV001219223 SCV001391149 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2021-09-07 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 492269). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with alanine at codon 595 of the PMS2 protein (p.Val595Ala). The valine residue is weakly conserved and there is a small physicochemical difference between valine and alanine.

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