ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2699C>G (p.Ser900Ter) (rs878853814)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000227488 SCV000284160 uncertain significance Lynch syndrome 2015-12-25 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the last exon of the MSH2 mRNA at codon 900 (p.Ser900*). While this is not anticipated to result in nonsense mediated decay, it is expected to create a truncated MSH2 protein. This variant is not present in population databases (ExAC no frequency) and has been reported in the literature in an individual with hereditary breast and ovarian cancer (HBOC) (PMID: 24549055). This nonsense change is located within a functionally conserved domain of the MSH2 protein that interacts with MSH6 and MSH3 (PMID: 18822302). Other truncating variants have been reported within this domain (PMID: 25200962, 21681552). In summary, this is a rare nonsense change that has been reported in an individual with breast and ovarian cancer but not seen in the general population. The evidence available at this time is insufficient to conclude whether or not this variant affects protein function or causes disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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