ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.2483T>G (p.Ile828Ser)

dbSNP: rs753067992
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000469497 SCV000548186 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2024-01-04 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 828 of the MSH2 protein (p.Ile828Ser). This variant is present in population databases (rs753067992, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MSH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 408488). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 33357406) indicates that this missense variant is not expected to disrupt MSH2 function with a negative predictive value of 80%. 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 2023-05-21 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, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV002284395 SCV002574486 uncertain significance not provided 2022-03-16 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 21120944, 18822302)
True Health Diagnostics RCV000572057 SCV000788033 uncertain significance Hereditary cancer-predisposing syndrome 2017-10-16 no assertion criteria provided clinical testing

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