ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.1769T>G (p.Leu590Ter) (rs1553662753)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000502589 SCV000592420 pathogenic Lynch syndrome criteria provided, single submitter clinical testing
Color RCV000774951 SCV000909038 pathogenic Hereditary cancer-predisposing syndrome 2018-03-25 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000502589 SCV000919641 pathogenic Lynch syndrome 2017-11-06 criteria provided, single submitter clinical testing Variant summary: The MLH1 c.1769T>G (p.Leu590X) variant results in a premature termination codon, predicted to cause a truncated or absent MLH1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.2141G>A/ p.Trp714X). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 246010 control chromosomes in gnomAD. This variant has been reported in multiple HNPCC individuals/families (Parc_2003, Sjursen_MLH_2016) and has been classified as pathogenic in the literature and by multiple clinical diagnostic laboratories/reputable databases. Taken together, this variant is classified as pathogenic.

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