ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.400A>G (p.Lys134Glu) (rs1060500710)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000461241 SCV000543645 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-11-05 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 134 of the MLH1 protein (p.Lys134Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MLH1-related disease. ClinVar contains an entry for this variant (Variation ID: 405430). An experimental study has shown that this variant does not abolish the MutLa-MutSa (MLH1-PMS2) interaction and preserves its mismatch repair activity in vitro (PMID: 17135187). 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 RCV000562753 SCV000662107 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-15 criteria provided, single submitter clinical testing Insufficient evidence

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