ClinVar Miner

Submissions for variant NM_002439.5(MSH3):c.3404T>G (p.Leu1135Arg)

gnomAD frequency: 0.00009  dbSNP: rs148947624
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000796880 SCV000936413 uncertain significance not provided 2025-01-18 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1135 of the MSH3 protein (p.Leu1135Arg). This variant is present in population databases (rs148947624, gnomAD 0.07%). 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: 643220). 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.
Ambry Genetics RCV002460107 SCV002618392 uncertain significance Hereditary cancer-predisposing syndrome 2024-01-04 criteria provided, single submitter clinical testing The p.L1135R variant (also known as c.3404T>G), located in coding exon 24 of the MSH3 gene, results from a T to G substitution at nucleotide position 3404. The leucine at codon 1135 is replaced by arginine, an amino acid with 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, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV000796880 SCV002819091 uncertain significance not provided 2022-07-08 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Baylor Genetics RCV003467359 SCV004197020 uncertain significance Endometrial carcinoma 2023-11-21 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005036145 SCV005666224 uncertain significance Endometrial carcinoma; Familial adenomatous polyposis 4 2024-03-16 criteria provided, single submitter clinical testing

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