ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1124C>T (p.Thr375Ile) (rs774539871)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000206649 SCV000261143 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-10-17 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 375 of the MSH2 protein (p.Thr375Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs774539871, ExAC 0.01%). This variant has not been reported in the literature in individuals with MSH2-related disease. ClinVar contains an entry for this variant (Variation ID: 220533). 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 C0"). 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 RCV000216074 SCV000278734 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-10 criteria provided, single submitter clinical testing Insufficient or conflicting evidence;Rare (0.1%) in general population databases (dbsnp, esp, 1000 genomes) ;In silico models in agreement (benign)
Color RCV000216074 SCV000908296 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-11 criteria provided, single submitter clinical testing

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