ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1595T>C (p.Val532Ala) (rs754778750)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000791418 SCV000548293 uncertain significance Hereditary nonpolyposis colon cancer 2018-12-23 criteria provided, single submitter clinical testing This sequence change replaces valine with alanine at codon 532 of the MSH2 protein (p.Val532Ala). The valine residue is weakly conserved and there is a small physicochemical difference between valine and alanine. This variant is present in population databases (rs754778750, ExAC 0.001%). This variant has been observed in an individual affected with clinical features of Lynch syndrome (PMID: 25980754). ClinVar contains an entry for this variant (Variation ID: 408539). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 RCV000572859 SCV000673872 uncertain significance Hereditary cancer-predisposing syndrome 2017-11-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000572859 SCV000684950 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-26 criteria provided, single submitter clinical testing
Mendelics RCV000477609 SCV000837835 uncertain significance Lynch syndrome 2018-07-02 criteria provided, single submitter clinical testing

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