ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.621A>G (p.Leu207=) (rs770554901)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000229196 SCV000284069 likely benign Lynch syndrome 2015-12-25 criteria provided, single submitter clinical testing
Color RCV000582109 SCV000689901 likely benign Hereditary cancer-predisposing syndrome 2017-09-28 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781535 SCV000919642 uncertain significance not specified 2018-02-09 criteria provided, single submitter clinical testing Variant summary: MLH1 c.621A>G alters a non-conserved nucleotide resulting in a synonymous change and 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant, c.621A>G, was observed with an allele frequency of 4.1e-06 in 245978 control chromosomes (gnomAD), which does not exceed the maximum expected allele frequency of 0.00071 for a pathogenic MLH1 variant. To our knowledge, no occurrence of c.621A>G in individuals affected with Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory submission via Clinvar (evaluation after 2014) classifies the variant as "likely benign." Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

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