ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.954C>T (p.His318=) (rs146777069)

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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 RCV000162434 SCV000212782 likely benign Hereditary cancer-predisposing syndrome 2014-12-11 criteria provided, single submitter clinical testing
Color RCV000162434 SCV000684884 likely benign Hereditary cancer-predisposing syndrome 2016-10-07 criteria provided, single submitter clinical testing
Counsyl RCV000662528 SCV000785092 likely benign Lynch syndrome II 2017-04-12 criteria provided, single submitter clinical testing
GeneDx RCV000420662 SCV000516838 benign not specified 2015-08-10 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 RCV000420662 SCV000917658 uncertain significance not specified 2018-07-31 criteria provided, single submitter clinical testing Variant summary: MLH1 c.954C>T 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-05 in 122004 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.954C>T has been reported in the literature in one individual affected with sporadic CRC. This report does not provide unequivocal conclusions about association of the variant with Lynch Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Invitae RCV000473453 SCV000556012 likely benign Hereditary nonpolyposis colon cancer 2017-11-02 criteria provided, single submitter clinical testing

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