ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.344T>A (p.Ile115Asn) (rs764120517)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000629699 SCV000750655 uncertain significance Hereditary nonpolyposis colon cancer 2017-11-19 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with asparagine at codon 115 of the MLH1 protein (p.Ile115Asn). The isoleucine residue is highly conserved and there is a large physicochemical difference between isoleucine and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with Lynch syndrome (Invitae). This variant has been reported in the Leiden Open-source Variation Database (PMID: 21520333). An experimental study showed that this missense change leads to an intermediate mutator phenotype in a yeast model (PMID: 15475387). 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.
Color RCV000777086 SCV000912770 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV000777086 SCV001181797 likely pathogenic Hereditary cancer-predisposing syndrome 2017-12-26 criteria provided, single submitter clinical testing In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Other data supporting pathogenic classification;Rarity in general population databases (dbsnp, esp, 1000 genomes);Structural Evidence

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