ClinVar Miner

Submissions for variant NM_002439.5(MSH3):c.2288G>T (p.Cys763Phe)

gnomAD frequency: 0.00001  dbSNP: rs373251342
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000799755 SCV000939431 uncertain significance not provided 2025-01-09 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 763 of the MSH3 protein (p.Cys763Phe). This variant is present in population databases (rs373251342, gnomAD 0.04%). This missense change has been observed in individual(s) with colorectal cancer (PMID: 28944238). ClinVar contains an entry for this variant (Variation ID: 645630). 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 tolerated. 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.
Sema4, Sema4 RCV002256515 SCV002536045 uncertain significance Hereditary cancer-predisposing syndrome 2022-01-22 criteria provided, single submitter curation
Ambry Genetics RCV002256515 SCV002734749 uncertain significance Hereditary cancer-predisposing syndrome 2023-11-14 criteria provided, single submitter clinical testing The p.C763F variant (also known as c.2288G>T), located in coding exon 16 of the MSH3 gene, results from a G to T substitution at nucleotide position 2288. The cysteine at codon 763 is replaced by phenylalanine, an amino acid with highly dissimilar properties. In one study, this alteration was identified in 1/1231 colorectal cancer cases and 0/93 controls (DeRycke MS et al. Mol Genet Genomic Med, 2017 Sep;5:553-569). This amino acid position is not well 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000799755 SCV004221071 uncertain significance not provided 2024-12-02 criteria provided, single submitter clinical testing The MSH3 c.2288G>T (p.Cys763Phe) variant has been reported in an individual with colorectal cancer (PMID: 28944238 (2017)). The frequency of this variant in the general population, 0.00035 (7/19906 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 conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant.
Baylor Genetics RCV004569562 SCV005053591 uncertain significance Endometrial carcinoma 2024-03-08 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005036160 SCV005666202 uncertain significance Endometrial carcinoma; Familial adenomatous polyposis 4 2024-06-18 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.