ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.3del (p.Met1fs)

dbSNP: rs1553408068
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000530042 SCV000624956 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2017-05-28 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide from exon 1 of the MSH6 mRNA (c.3delG), affecting the initiator methionine. While this variant may disrupt protein translation of the MSH6 mRNA, an alternate in-frame methionine downstream of the original initiator codon located at codon 100 could potentially rescue translation initiation. However, experimental studies have not been performed to determine if an alternative initiator codon is utilized. In summary, this variant has uncertain impact on MSH6 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals with a MSH6-related disease. This variant is not present in population databases (ExAC no frequency).
Ambry Genetics RCV001021626 SCV001183266 pathogenic Hereditary cancer-predisposing syndrome 2021-07-13 criteria provided, single submitter clinical testing The c.3delG pathogenic mutation, located in coding exon 1 of the MSH6 gene, results from a deletion of one nucleotide at nucleotide position 3. This alters the methionine residue at the initiation codon (p.M1?). While this specific alteration has not been reported in the literature to date, several other missense pathogenic mutations (c.1A>G, c.3G>C, c.3G>T) that alter the methionine residue at the initiation codon in MSH6 (p.M1?) have been identified in individuals whose Lynch-associated tumors displayed absent MSH6 staining on immunohistochemistry (IHC) (Ambry internal data). Since sequence variations that modify the initiation codon (ATG) are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame, this alteration is interpreted as a disease-causing mutation.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.