ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.998A>T (p.Asp333Val)

dbSNP: rs1187390273
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001019957 SCV001181377 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-18 criteria provided, single submitter clinical testing The p.D333V variant (also known as c.998A>T), located in coding exon 10 of the PMS2 gene, results from an A to T substitution at nucleotide position 998. The aspartic acid at codon 333 is replaced by valine, an amino acid with highly dissimilar 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.
All of Us Research Program, National Institutes of Health RCV004004593 SCV004838948 uncertain significance Lynch syndrome 2024-01-03 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with valine at codon 333 of the PMS2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, 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.

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