ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.1846C>T (p.Pro616Ser)

dbSNP: rs587782627
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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 RCV000132012 SCV000187071 likely benign Hereditary cancer-predisposing syndrome 2022-08-08 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV000629677 SCV000750633 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2023-10-12 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 616 of the MSH2 protein (p.Pro616Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with unspecified cancer (PMID: 31386297). ClinVar contains an entry for this variant (Variation ID: 142665). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 33357406) indicates that this missense variant is not expected to disrupt MSH2 function. 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.
Cancer Genomics Group, Japanese Foundation For Cancer Research RCV001030712 SCV001193634 uncertain significance Hereditary breast ovarian cancer syndrome 2019-05-01 criteria provided, single submitter research
Revvity Omics, Revvity RCV003129784 SCV003808945 uncertain significance not provided 2019-09-07 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003998127 SCV004829763 uncertain significance Lynch syndrome 2023-04-03 criteria provided, single submitter clinical testing This missense variant replaces proline with serine at codon 616 of the MSH2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). This variant does not impact MSH2 function in a 6-thioguanine sensitivity assay in haploid human cells (internally defined LOF score threshold <= -1.32, PMID: 33357406). This variant has been reported in two individuals affected with unspecified cancer (PMID: 31386297). 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.

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