ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2579C>T (p.Ser860Leu) (rs63750849)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000575134 SCV000662244 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000575134 SCV000690081 likely benign Hereditary cancer-predisposing syndrome 2017-09-18 criteria provided, single submitter clinical testing
GeneDx RCV000438978 SCV000521068 likely benign not specified 2016-05-11 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.
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000076508 SCV000107537 likely benign Lynch syndrome 2013-09-05 reviewed by expert panel research Multifactorial likelihood analysis posterior probability 0.001-0.049
Invitae RCV000524395 SCV000284154 uncertain significance Hereditary nonpolyposis colon cancer 2018-11-08 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 860 of the MSH2 protein (p.Ser860Leu). The serine residue is weakly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs63750849, ExAC 0.001%). This variant has not been reported in the literature in individuals with MSH2-related disease. ClinVar contains an entry for this variant (Variation ID: 91006). An algorithm developed to predict the effect of missense changes in mismatch repair genes (PMID: 22290698), suggests that this variant is neutral. This prediction is further supported by an experimental study that demonstrates this variant preserves MSH2 DNA repair function in a cell free assay (PMID: 22102614). 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.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000438978 SCV000539691 uncertain significance not specified 2016-10-20 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Classified as LB by InSiGHT expert panel. Another variant at the same position (Ser860X) has been classified as P.

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