ClinVar Miner

Submissions for variant NM_002439.5(MSH3):c.1256C>T (p.Ser419Leu)

gnomAD frequency: 0.00001  dbSNP: rs578113271
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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 RCV001051206 SCV001215349 uncertain significance not provided 2024-12-28 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 419 of the MSH3 protein (p.Ser419Leu). This variant is present in population databases (rs578113271, gnomAD 0.007%). 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: 847620). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The leucine 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 RCV002416387 SCV002678470 likely benign Hereditary cancer-predisposing syndrome 2020-11-20 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Fulgent Genetics, Fulgent Genetics RCV005036339 SCV005666178 uncertain significance Endometrial carcinoma; Familial adenomatous polyposis 4 2024-03-21 criteria provided, single submitter clinical testing

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