ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.861C>G (p.Asn287Lys) (rs63750421)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000527545 SCV000625203 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2017-03-21 criteria provided, single submitter clinical testing This sequence change replaces asparagine with lysine at codon 287 of the MLH1 protein (p.Asn287Lys). The asparagine residue is moderately conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MLH1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Color RCV000777184 SCV000912875 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV000777184 SCV001179274 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-03 criteria provided, single submitter clinical testing Insufficient evidence

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