ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1607A>T (p.Asn536Ile) (rs201722703)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000532887 SCV000625288 uncertain significance Hereditary nonpolyposis colon cancer 2019-11-15 criteria provided, single submitter clinical testing This sequence change replaces asparagine with isoleucine at codon 536 of the MSH2 protein (p.Asn536Ile). The asparagine residue is highly conserved and there is a large physicochemical difference between asparagine and isoleucine. 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: 455510). 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 disruptive, 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.
Integrated Genetics/Laboratory Corporation of America RCV000781553 SCV000919687 uncertain significance not specified 2017-10-10 criteria provided, single submitter clinical testing Variant summary: The MSH2 c.1607A>T (p.Asn536Ile) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant is absent in 246192 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.

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