ClinVar Miner

Submissions for variant NM_002439.5(MSH3):c.2785A>T (p.Ile929Phe)

gnomAD frequency: 0.00001  dbSNP: rs759266003
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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 RCV001239931 SCV001412835 uncertain significance not provided 2023-12-18 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 929 of the MSH3 protein (p.Ile929Phe). This variant is present in population databases (no rsID available, gnomAD 0.002%). This missense change has been observed in individual(s) with colorectal cancer (PMID: 25142776). ClinVar contains an entry for this variant (Variation ID: 965474). 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 RCV002436946 SCV002748270 uncertain significance Hereditary cancer-predisposing syndrome 2024-01-04 criteria provided, single submitter clinical testing The p.I929F variant (also known as c.2785A>T), located in coding exon 20 of the MSH3 gene, results from an A to T substitution at nucleotide position 2785. The isoleucine at codon 929 is replaced by phenylalanine, an amino acid with highly similar properties. This alteration has been reported as an uncertain variant in a cohort of 152 colorectal cancer patients (Kraus C et al. Int J Cancer, 2015 Mar;136:E559-68). 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.
Baylor Genetics RCV003469453 SCV004195162 uncertain significance Endometrial carcinoma 2023-06-26 criteria provided, single submitter clinical testing

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