ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.1877del (p.Phe626fs)

dbSNP: rs63750152
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000075396 SCV000106390 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Ambry Genetics RCV000571618 SCV000676069 pathogenic Hereditary cancer-predisposing syndrome 2018-11-14 criteria provided, single submitter clinical testing The c.1877delT pathogenic mutation, located in coding exon 16 of the MLH1 gene, results from a deletion of one nucleotide at nucleotide position 1877, causing a translational frameshift with a predicted alternate stop codon (p.F626Sfs*11). This mutation has been detected in a patient diagnosed with colorectal cancer at age 40y who reported a family history of early-onset colorectal and endometrial cancer (Samowitz WS et al. Gastroenterology. 2001 Oct;121(4):830-8). 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.
Invitae RCV000692128 SCV000819937 pathogenic Hereditary nonpolyposis colorectal neoplasms 2020-03-12 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 an individual affected with colon cancer (PMID: 11606497). ClinVar contains an entry for this variant (Variation ID: 89917). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Phe626Serfs*11) in the MLH1 gene. It is expected to result in an absent or disrupted protein product.
Myriad Genetics, Inc. RCV003451076 SCV004186312 pathogenic Colorectal cancer, hereditary nonpolyposis, type 2 2023-07-24 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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