ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1714_1715delinsAT (p.Glu572Ile) (rs1558514635)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000688354 SCV000815961 uncertain significance Hereditary nonpolyposis colon cancer 2018-02-17 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with isoleucine at codon 572 of the MSH2 protein (p.Glu572Ile). The glutamic acid residue is moderately conserved and there is a moderate physicochemical difference between glutamic acid 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. 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: "Deleterous"; PolyPhen-2: "Probably Damaging"; 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.
Integrated Genetics/Laboratory Corporation of America RCV000780439 SCV000917688 uncertain significance not specified 2017-11-09 criteria provided, single submitter clinical testing Variant summary: The MSH2 c.1714_1715delinsAT (p.Glu572Ile) variant involves the alteration of a replacement of two nucleotides. One in silico tool predicts a damaging outcome for this variant. This variant is absent in 245814 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. One LCA specimen also carries likely pathogenic APC c.5152_5153delinsA, supporting the potential benign nature of the variant. 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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