ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.463del (p.Leu155fs)

dbSNP: rs2082049708
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001213971 SCV001385633 pathogenic Hereditary nonpolyposis colorectal neoplasms 2021-06-11 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MLH1 are known to be pathogenic (PMID: 15713769, 24362816). This variant has been observed in a family with clinical features of Lynch syndrome (PMID: 24710284). This variant is also known as c.462delC in the literature. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Leu155Phefs*5) in the MLH1 gene. It is expected to result in an absent or disrupted protein product.
Ambry Genetics RCV002339558 SCV002640256 pathogenic Hereditary cancer-predisposing syndrome 2019-02-27 criteria provided, single submitter clinical testing The c.463delC pathogenic mutation, located in coding exon 6 of the MLH1 gene, results from a deletion of one nucleotide at nucleotide position 463, causing a translational frameshift with a predicted alternate stop codon (p.L155Ffs*5). This pathogenic mutation, referred to as c.462delC by authors, was reported in one Chinese individual who met Amsterdam criteria (Liu Y et al. PLoS ONE. 2014 Apr;9:e94170). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc. RCV003449675 SCV004186542 pathogenic Colorectal cancer, hereditary nonpolyposis, type 2 2023-07-14 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

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