ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.1252_1253del (p.Asp418fs)

dbSNP: rs63751118
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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) RCV000075159 SCV000106150 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Labcorp Genetics (formerly Invitae), Labcorp RCV000815020 SCV000955460 pathogenic Hereditary nonpolyposis colorectal neoplasms 2022-11-02 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: 89686). This premature translational stop signal has been observed in individual(s) with Lynch syndrome (PMID: 16451135). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asp418Tyrfs*3) 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).
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001284160 SCV001469788 pathogenic not provided 2024-08-20 criteria provided, single submitter clinical testing The MLH1 c.1252_1253del (p.Asp418Tyrfs*3) variant alters the translational reading frame of the MLH1 mRNA and causes the premature termination of MLH1 protein synthesis. This variant has been reported in the published literature in multiple individuals with Lynch syndrome or Lynch-related conditions (PMIDs: 16451135 (2006), 20007843 (2010), 24333619 (2014), 30877237 (2019)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as pathogenic.
Myriad Genetics, Inc. RCV003451015 SCV004187737 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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