ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.1165C>T (p.Arg389Trp) (rs61751644)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165994 SCV000216752 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-16 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
University of Washington Department of Laboratory Medicine, University of Washington RCV000075132 SCV000266176 uncertain significance Lynch syndrome 2015-11-20 criteria provided, single submitter clinical testing
Invitae RCV000627719 SCV000543540 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2020-01-07 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 389 of the MLH1 protein (p.Arg389Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (rs61751644, ExAC no frequency). This variant has been reported in individuals with colorectal cancer (PMID: 11606497, 19575290). ClinVar contains an entry for this variant (Variation ID: 89661). In vitro experimental studies have shown that this missense change retains localization of the MLH1 protein to the nucleus and interaction with PMS2 and EXO1 proteins, but may affect mismatch repair activity (PMID: 22753075). The clinical significance of these findings is unclear. 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.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000582826 SCV000691861 uncertain significance not specified no assertion criteria provided clinical testing

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