ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1122G>C (p.Gln374His) (rs370378607)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115493 SCV000149402 uncertain significance not provided 2014-02-20 criteria provided, single submitter clinical testing This variant is denoted MSH2 c.1122G>C at the cDNA level, p.Gln374His (Q374H) at the protein level, and results in the change of a Glutamine to a Histidine (CAG>CAC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH2 Gln374His was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. This variant is a semi-conservative substitution in which a neutral polar amino acid is replaced with a positive polar one, altering a position that is well conserved throughout evolution and is located in the Lever domain (Lutzen 2008). Multiple in silico algorithms predict that this variant may be damaging to protein structure and function. Based on the currently available information, we consider MSH2 Gln374His to be a variant of uncertain significance.
Invitae RCV000122979 SCV000166259 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-10-20 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 374 of the MSH2 protein (p.Gln374His). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and histidine. This variant is present in population databases (rs370378607, 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: 127626). 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: "Deleterious"; PolyPhen-2: "Possibly 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.
Color RCV000580948 SCV000684906 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-10 criteria provided, single submitter clinical testing
Ambry Genetics RCV000580948 SCV001170018 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-23 criteria provided, single submitter clinical testing Insufficient evidence

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