ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.1652A>G (p.Asn551Ser) (rs63750271)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000781995 SCV000920452 benign Lynch syndrome 2018-10-18 reviewed by expert panel curation Multifactorial likelihood analysis posterior probability < 0.001 (0.00084)
Invitae RCV000228672 SCV000284023 uncertain significance Hereditary nonpolyposis colon cancer 2018-08-28 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 551 of the MLH1 protein (p.Asn551Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with colon cancer (PMID: 21404117). ClinVar contains an entry for this variant (Variation ID: 237316). Experimental studies have shown that this missense change does not significantly affect MLH1 protein function (PMID: 21404117). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000563396 SCV000662030 uncertain significance Hereditary cancer-predisposing syndrome 2017-03-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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