ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.2400T>C (p.Val800=) (rs267608071)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000491664 SCV000580206 likely benign Hereditary cancer-predisposing syndrome 2016-04-13 criteria provided, single submitter clinical testing
Color RCV000491664 SCV000690258 likely benign Hereditary cancer-predisposing syndrome 2016-04-29 criteria provided, single submitter clinical testing
Counsyl RCV000663185 SCV000786356 likely benign Hereditary nonpolyposis colorectal cancer type 5 2018-04-16 criteria provided, single submitter clinical testing
GeneDx RCV000427895 SCV000513691 likely benign not specified 2017-04-10 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.
Integrated Genetics/Laboratory Corporation of America RCV000427895 SCV000917782 likely benign not specified 2018-10-23 criteria provided, single submitter clinical testing Variant summary: MSH6 c.2400T>C alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4.1e-06 in 245490 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.2400T>C, has been reported in the literature in one individual affected with Lynch Syndrome which had a co-occurrence with another pathogenic MSH2 variant, c.229_230delAG (p.Ser77fsX4), providing supporting evidence for a benign role (Perez-Cabornero_2013). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000074745 SCV000107954 uncertain significance Lynch syndrome 2013-09-05 reviewed by expert panel research Insufficient evidence
Invitae RCV000524142 SCV000283749 likely benign Hereditary nonpolyposis colon cancer 2017-11-13 criteria provided, single submitter clinical testing

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