ClinVar Miner

Submissions for variant NM_002439.5(MSH3):c.1327G>A (p.Ala443Thr)

gnomAD frequency: 0.00001  dbSNP: rs752066199
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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 RCV001364259 SCV001560394 uncertain significance not provided 2024-09-08 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 443 of the MSH3 protein (p.Ala443Thr). This variant is present in population databases (rs752066199, gnomAD 0.0009%). 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: 1055567). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
Ambry Genetics RCV002384519 SCV002690503 uncertain significance Hereditary cancer-predisposing syndrome 2023-10-02 criteria provided, single submitter clinical testing The p.A443T variant (also known as c.1327G>A), located in coding exon 8 of the MSH3 gene, results from a G to A substitution at nucleotide position 1327. The alanine at codon 443 is replaced by threonine, an amino acid with similar 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.
GeneDx RCV001364259 SCV005387226 uncertain significance not provided 2024-04-22 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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