ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.793C>A (p.Arg265Ser) (rs63751194)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000567864 SCV000664835 pathogenic Hereditary cancer-predisposing syndrome 2017-01-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other strong data supporting pathogenic classification,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Deficient protein function in appropriate functional assay(s)
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000075871 SCV000592379 pathogenic Lynch syndrome 2013-04-10 criteria provided, single submitter clinical testing
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000075871 SCV000106885 pathogenic Lynch syndrome 2018-10-18 reviewed by expert panel curation Paper by Van der Klift et al. 2015 shows aberrant splicing (exon 10 exclusion) in patient sample and minigene assay, confirmed by minigene assay in Soukarieh et al., 2016 (Plos Genet).
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000202126 SCV000257116 pathogenic not provided no assertion criteria provided research
University of Washington Department of Laboratory Medicine,University of Washington RCV000075871 SCV000887314 likely pathogenic Lynch syndrome 2018-05-01 criteria provided, single submitter clinical testing MLH1 NM_000249.3:c.793C>A has a 97.7% probability of pathogenicity based on combining prior probability from public data with a likelihood ratio of 1.56 to 1, generated from evidence of seeing this as a somatic mutation in a tumor without loss of heterozygosity at the MLH1 locus. See Shirts et al 2018, PMID 29887214.

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