ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.3609_3612del (p.His1203fs)

dbSNP: rs587779274
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000074893 SCV000108105 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV002267831 SCV002552351 pathogenic not provided 2023-08-15 criteria provided, single submitter clinical testing
Invitae RCV002514332 SCV003524642 pathogenic Hereditary nonpolyposis colorectal neoplasms 2022-09-01 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant is also known as c.3607_3610delCATG or c.3603_3606delAGTG. This premature translational stop signal has been observed in individual(s) with MSH6-related conditions (PMID: 16283678, 22495361). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.His1203Glnfs*12) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816).
Myriad Genetics, Inc. RCV003450975 SCV004188279 pathogenic Lynch syndrome 5 2023-08-24 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
PreventionGenetics, part of Exact Sciences RCV004537279 SCV004711276 pathogenic MSH6-related disorder 2024-01-18 criteria provided, single submitter clinical testing The MSH6 c.3609_3612delTGCA variant is predicted to result in a frameshift and premature protein termination (p.His1203Glnfs*12). This variant along with a second variant in this gene was reported in at least one individual with hereditary nonpolyposis colorectal cancer (reported as c.3607_3610delCATG, Okkels et al 2012. PubMed ID: 22495361). This variant in the compound heterozygous condition along with a second variant in this gene was reported in two siblings with Neurofibromatosis, type 1 (Ostergaard et al 2005. PubMed ID: 16283678). In the homozygous condition, this variant was reported in several individuals with clinical features overlapping with constitutional mismatch repair deficiency and Tuberous Sclerosis complex (reported as c.3603_3606del, Rootman et al. 2020. PubMed ID: 31730237). This variant has not been reported in a large population database, indicating this variant is rare. In ClinVar, this variant was reported as pathogenic (https://preview.ncbi.nlm.nih.gov/clinvar/variation/89425/). This variant is interpreted as pathogenic.

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