ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1379T>C (p.Met460Thr) (rs1553361303)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000567509 SCV000673868 uncertain significance Hereditary cancer-predisposing syndrome 2018-11-14 criteria provided, single submitter clinical testing The p.M460T variant (also known as c.1379T>C), located in coding exon 8 of the MSH2 gene, results from a T to C substitution at nucleotide position 1379. The methionine at codon 460 is replaced by threonine, 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.
Color RCV000567509 SCV000689981 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-06 criteria provided, single submitter clinical testing
Invitae RCV000685208 SCV000812681 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-10-21 criteria provided, single submitter clinical testing This sequence change replaces methionine with threonine at codon 460 of the MSH2 protein (p.Met460Thr). The methionine residue is moderately conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 485825). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759100 SCV000888205 uncertain significance not provided 2018-02-08 criteria provided, single submitter clinical testing

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