ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2407A>G (p.Thr803Ala) (rs63751168)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000543029 SCV000625378 uncertain significance Hereditary nonpolyposis colon cancer 2017-07-28 criteria provided, single submitter clinical testing This sequence change replaces threonine with alanine at codon 803 of the MSH2 protein (p.Thr803Ala). The threonine residue is highly conserved and there is a small physicochemical difference between threonine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with gastric cancer, however, the germline nature of this variant was not ascertained (PMID: 21528233). 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: "Benign"; Align-GVGD: "Class C0"). In addition, an algorithm developed specifically for the MSH2 gene classifies this missense change as a variant of uncertain significance (PMID: 18383312). However, 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.
Integrated Genetics/Laboratory Corporation of America RCV000588000 SCV000696248 uncertain significance not provided 2017-05-08 criteria provided, single submitter clinical testing Variant summary: The MSH2 c.2407A>G (p.Thr803Ala) variant involves the alteration of a conserved nucleotide. 3/5 in silico tools predict a damaging outcome for this variant. This variant is absent in 121386 control chromosomes and has been reported in the literature, without strong evidence for causality. The variant has not been reported in databases, nor evaluated via any funcitonal studies. Therefore, this variant is classified as VUS until additional evidence becomes available.
Ambry Genetics RCV001015432 SCV001176263 uncertain significance Hereditary cancer-predisposing syndrome 2019-05-24 criteria provided, single submitter clinical testing Insufficient evidence
Cancer Genomics Group,Japanese Foundation For Cancer Research RCV001030715 SCV001193637 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-05-01 criteria provided, single submitter research
Color RCV001015432 SCV001347187 uncertain significance Hereditary cancer-predisposing syndrome 2020-03-24 criteria provided, single submitter clinical testing

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