ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.894G>C (p.Gln298His) (rs587781397)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129243 SCV000184002 uncertain significance Hereditary cancer-predisposing syndrome 2019-10-03 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Color RCV000129243 SCV000685137 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-15 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000586127 SCV000696293 uncertain significance not provided 2017-03-03 criteria provided, single submitter clinical testing Variant summary: The MSH2 c.894G>C (p.Gln298His) variant involves the alteration of a non-conserved nucleotide, resulting in a missense substitution. The variant is found outside of, but very near to, two known functional domains (Connector domain [aa153-289] and Core domain [aa303-645]; InterPro). 3/4 in silico tools predict a damaging outcome for this variant (SNPs&GO not captured due to low reliability index). This variant is absent from the large control population database ExAC (0/121246 control chromosomes). In addition, one clinical diagnostic laboratory classified this variant as uncertain significance. One publication has cited the variant in a patient with cancer of the cecum, but co-segregation and family history data was not provided (Pearlman_JAMA_2016). Taken together, this variant is classified as VUS until more information becomes available.
Invitae RCV000701906 SCV000830729 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-11-25 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 298 of the MSH2 protein (p.Gln298His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine. 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. ClinVar contains an entry for this variant (Variation ID: 140960). 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: "Probably Damaging"; Align-GVGD: "Class C15"). 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.
True Health Diagnostics RCV000129243 SCV000805270 uncertain significance Hereditary cancer-predisposing syndrome 2018-04-05 no assertion criteria provided clinical testing

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