ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.328A>C (p.Lys110Gln) (rs587779970)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115526 SCV000149435 uncertain significance not provided 2018-07-06 criteria provided, single submitter clinical testing This variant is denoted MSH2 c.328A>C at the cDNA level, p.Lys110Gln (K110Q) at the protein level, and results in the change of a Lysine to a Glutamine (AAG>CAG). This variant was observed in an individual with both colon and rectal cancers (de Rosa 2016). MSH2 Lys110Gln was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the mismatch binding domain (L?tzen 2008, Kansikas 2011). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether MSH2 Lys110Gln is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000475276 SCV000548227 uncertain significance Hereditary nonpolyposis colon cancer 2018-12-21 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamine at codon 110 of the MSH2 protein (p.Lys110Gln). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with colorectal cancer (PMID: 27432916). ClinVar contains an entry for this variant (Variation ID: 127642). 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 RCV000567258 SCV000662237 uncertain significance Hereditary cancer-predisposing syndrome 2018-02-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000567258 SCV000685079 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-20 criteria provided, single submitter clinical testing

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