ClinVar Miner

Submissions for variant NM_000535.7(PMS2):c.1139T>G (p.Val380Gly)

gnomAD frequency: 0.00001  dbSNP: rs748971523
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000775363 SCV000909658 uncertain significance Hereditary cancer-predisposing syndrome 2021-04-21 criteria provided, single submitter clinical testing This missense variant replaces valine with glycine at codon 380 of the PMS2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 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 hereditary cancer in the literature. This variant has been identified in 3/251238 chromosomes 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.
Ambry Genetics RCV000775363 SCV001170123 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-01 criteria provided, single submitter clinical testing The p.V380G variant (also known as c.1139T>G), located in coding exon 10 of the PMS2 gene, results from a T to G substitution at nucleotide position 1139. The valine at codon 380 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is poorly 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.
Invitae RCV001067061 SCV001232093 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2023-09-29 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 630207). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This variant is present in population databases (rs748971523, gnomAD 0.006%). This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 380 of the PMS2 protein (p.Val380Gly). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PMS2 protein function. 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.
Baylor Genetics RCV003461037 SCV004205423 uncertain significance Lynch syndrome 4 2023-09-29 criteria provided, single submitter clinical testing

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