ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.2238dup (p.Leu747fs)

dbSNP: rs1553413599
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000558657 SCV000624737 pathogenic Hereditary nonpolyposis colorectal neoplasms 2021-05-13 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 24362816, 18269114). This variant has been observed in an individual affected with constitutional mismatch repair deficiency syndrome (PMID: 30013564). ClinVar contains an entry for this variant (Variation ID: 455182). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Leu747Serfs*9) in the MSH6 gene. It is expected to result in an absent or disrupted protein product.
Ambry Genetics RCV002431514 SCV002730969 pathogenic Hereditary cancer-predisposing syndrome 2019-02-08 criteria provided, single submitter clinical testing The c.2238dupT variant, located in coding exon 4 of the MSH6 gene, results from a duplication of T at nucleotide position 2238, causing a translational frameshift with a predicted alternate stop codon (p.L747Sfs*9). This mutation has been reported in conjunction with another MSH6 alteration in a patient who was diagnosed with medulloblastoma at age 6 and who was also found to have a cafe au lait macule (Tesch VK et al. Front Immunol, 2018 Jul;9:1506). 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.
Myriad Genetics, Inc. RCV003449503 SCV004185656 pathogenic Lynch syndrome 5 2023-08-16 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
All of Us Research Program, National Institutes of Health RCV004003673 SCV004841323 pathogenic Lynch syndrome 2023-10-23 criteria provided, single submitter clinical testing This variant inserts 1 nucleotide in exon 4 of the MSH6 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been observed in an individual affected with Constitutional mismatch repair deficiency who also carried the c.2980T>A, p.(Tyr994Asn) variant in MSH6 (PMID: 30013564). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MSH6 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

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.