ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.1915C>T (p.His639Tyr) (rs28929484)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000030246 SCV000107343 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Variant causes splicing aberration (full inactivation variant allele)
Ambry Genetics RCV000491611 SCV000580461 pathogenic Hereditary cancer-predisposing syndrome 2019-01-09 criteria provided, single submitter clinical testing Functionally-validated splicing mutation;Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;RNA Studies
Invitae RCV001204094 SCV001375285 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-10-08 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 639 of the MSH2 protein (p.His639Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with clinical features of hereditary non-polyposis colorectal cancer (PMID: 8062247, 8261515, 11555625, 16395668, 9718327, 11920458). ClinVar contains an entry for this variant (Variation ID: 1756). This variant has been reported to affect MSH2 protein function (PMID: 17720936). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 16395668, 8062247). 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.
OMIM RCV000001826 SCV000021982 pathogenic Lynch syndrome I 1993-12-17 no assertion criteria provided literature only
Integrated Genetics/Laboratory Corporation of America RCV000030246 SCV000052913 likely pathogenic Lynch syndrome 2015-10-02 no assertion criteria provided clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202104 SCV000257159 pathogenic not provided no assertion criteria provided clinical testing

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