ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1060G>T (p.Val354Phe)

gnomAD frequency: 0.00001  dbSNP: rs750984324
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000812739 SCV000953062 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2020-06-28 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with PMS2-related disease. 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant is present in population databases (rs750984324, ExAC 0.003%). This sequence change replaces valine with phenylalanine at codon 354 of the PMS2 protein (p.Val354Phe). The valine residue is weakly conserved and there is a small physicochemical difference between valine and phenylalanine.
Clinical Genetics Laboratory, Skane University Hospital Lund RCV004697005 SCV005197206 uncertain significance not provided 2022-05-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV004944200 SCV005472519 uncertain significance Hereditary cancer-predisposing syndrome 2024-10-04 criteria provided, single submitter clinical testing The p.V354F variant (also known as c.1060G>T), located in coding exon 10 of the PMS2 gene, results from a G to T substitution at nucleotide position 1060. The valine at codon 354 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.

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