ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1396C>T (p.His466Tyr) (rs876658457)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000217983 SCV000273702 uncertain significance Hereditary cancer-predisposing syndrome 2020-08-12 criteria provided, single submitter clinical testing The p.H466Y variant (also known as c.1396C>T), located in coding exon 9 of the MSH2 gene, results from a C to T substitution at nucleotide position 1396. The histidine at codon 466 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is highly 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.
Invitae RCV000537839 SCV000625258 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-10-22 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 466 of the MSH2 protein (p.His466Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MSH2-related disease. ClinVar contains an entry for this variant (Variation ID: 230236). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C65"). 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.
Color RCV000217983 SCV000903694 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-25 criteria provided, single submitter clinical testing

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