ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.1896+7C>T (rs863224339)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000198196 SCV000253136 likely benign Hereditary nonpolyposis colorectal neoplasms 2020-11-10 criteria provided, single submitter clinical testing
Counsyl RCV000411286 SCV000489668 likely benign Lynch syndrome II 2016-11-02 criteria provided, single submitter clinical testing
GeneDx RCV000419669 SCV000533051 likely benign not specified 2016-10-19 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.
Color Health, Inc RCV000579905 SCV000684781 likely benign Hereditary cancer-predisposing syndrome 2016-09-15 criteria provided, single submitter clinical testing
Mendelics RCV000411286 SCV001136428 likely benign Lynch syndrome II 2019-05-28 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000419669 SCV001362940 uncertain significance not specified 2019-03-08 criteria provided, single submitter clinical testing Variant summary: MLH1 c.1896+7C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 246158 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1896+7C>T in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have 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 likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.

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