ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2483T>G (p.Ile828Ser) (rs753067992)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000469497 SCV000548186 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-11-23 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with serine at codon 828 of the MSH2 protein (p.Ile828Ser). The isoleucine residue is highly conserved and there is a large physicochemical difference between isoleucine and serine. This variant is present in population databases (rs753067992, ExAC 0.002%). This variant has not been reported in the literature in individuals with MSH2-related disease. ClinVar contains an entry for this variant (Variation ID: 408488). 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.
Ambry Genetics RCV000572057 SCV000662269 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-29 criteria provided, single submitter clinical testing The p.I828S variant (also known as c.2483T>G), located in coding exon 15 of the MSH2 gene, results from a T to G substitution at nucleotide position 2483. The isoleucine at codon 828 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. In addition, this alteration is predicted to be deleterious by MAPP-MMR in silico analyses (Chao E et al. Hum Mutat. 2008 Jun;29(6):852-60). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
True Health Diagnostics RCV000572057 SCV000788033 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-16 no assertion criteria provided clinical testing

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