ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2164G>A (p.Val722Ile) (rs587781996)

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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 RCV000130409 SCV000185271 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-26 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000168465 SCV000219164 uncertain significance Hereditary nonpolyposis colon cancer 2018-12-15 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 722 of the MSH2 protein (p.Val722Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs587781996, ExAC 0.02%). This variant has been observed in individuals with colorectal cancer (PMID: 19697156, 27601186, 10612827). However, in one of these individuals a pathogenic allele was also identified in MSH2, which suggests that this c.2164G>A variant was not the primary cause of disease (PMID: 10612827). ClinVar contains an entry for this variant (Variation ID: 141769). Experimental studies have shown that this missense change behaves as wild-type in a mismatch repair (MMR) activity and protein stability assay (PMID: 19697156). 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.
GeneDx RCV000487305 SCV000565993 likely benign not specified 2018-03-09 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Color RCV000130409 SCV000910890 likely benign Hereditary cancer-predisposing syndrome 2015-03-12 criteria provided, single submitter clinical testing
GenomeConnect, ClinGen RCV000509191 SCV000607173 not provided not provided no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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