ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.1101del (p.Ser368fs)

dbSNP: rs63750715
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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) RCV000075112 SCV000106103 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Ambry Genetics RCV002426629 SCV002742581 pathogenic Hereditary cancer-predisposing syndrome 2018-07-18 criteria provided, single submitter clinical testing The c.1101delC pathogenic mutation, located in coding exon 12 of the MLH1 gene, results from a deletion of one nucleotide at nucleotide position 1101, causing a translational frameshift with a predicted alternate stop codon (p.S368Rfs*33). This mutation has been identified in a high-risk CRC family (Terdiman JP et al. Gastroenterology, 2001 Jan;120:21-30). In addition to the published data, 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 RCV002514336 SCV003525418 pathogenic Hereditary nonpolyposis colorectal neoplasms 2022-02-01 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 89642). This premature translational stop signal has been observed in individual(s) with colorectal cancer (PMID: 11208710). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser368Argfs*33) in the MLH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MLH1 are known to be pathogenic (PMID: 15713769, 24362816).
Myriad Genetics, Inc. RCV003451005 SCV004187625 pathogenic Colorectal cancer, hereditary nonpolyposis, type 2 2023-07-19 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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