ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.317G>C (p.Arg106Thr) (rs41295286)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000567001 SCV000669870 uncertain significance Hereditary cancer-predisposing syndrome 2017-07-06 criteria provided, single submitter clinical testing The p.R106T variant (also known as c.317G>C), located in coding exon 2 of the MSH2 gene, results from a G to C substitution at nucleotide position 317. The arginine at codon 106 is replaced by threonine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. In addition, this alteration is predicted to be benign by MAPP-MMR in silico analyses (Chao EC et al. Hum. Mutat. 2008 Jun;29:852-60). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Health, Inc RCV000567001 SCV000905153 uncertain significance Hereditary cancer-predisposing syndrome 2020-06-05 criteria provided, single submitter clinical testing This missense variant replaces arginine with threonine at codon 106 of the MSH2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Invitae RCV000793779 SCV000933151 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2018-12-05 criteria provided, single submitter clinical testing This sequence change replaces arginine with threonine at codon 106 of the MSH2 protein (p.Arg106Thr). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and threonine. 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 conditions. ClinVar contains an entry for this variant (Variation ID: 483749). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; 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.

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