ClinVar Miner

Submissions for variant NM_002439.5(MSH3):c.923A>T (p.Lys308Met)

gnomAD frequency: 0.00003  dbSNP: rs746243211
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000814562 SCV000954975 uncertain significance not provided 2024-11-13 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with methionine, which is neutral and non-polar, at codon 308 of the MSH3 protein (p.Lys308Met). This variant is present in population databases (rs746243211, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with MSH3-related conditions. ClinVar contains an entry for this variant (Variation ID: 657862). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 RCV001019059 SCV001180367 uncertain significance Hereditary cancer-predisposing syndrome 2023-11-24 criteria provided, single submitter clinical testing The p.K308M variant (also known as c.923A>T), located in coding exon 6 of the MSH3 gene, results from an A to T substitution at nucleotide position 923. The lysine at codon 308 is replaced by methionine, an amino acid with similar 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.
Sema4, Sema4 RCV001019059 SCV002536555 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-19 criteria provided, single submitter curation
Baylor Genetics RCV003461224 SCV004196962 uncertain significance Endometrial carcinoma 2024-03-25 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000814562 SCV004221126 uncertain significance not provided 2023-07-29 criteria provided, single submitter clinical testing This variant has not been reported in the published literature. The frequency of this variant in the general population, 0.000085 (3/35434 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV004596354 SCV005090640 uncertain significance not specified 2024-07-31 criteria provided, single submitter clinical testing

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