ClinVar Miner

Submissions for variant NM_002471.4(MYH6):c.3437dup (p.Glu1147fs)

dbSNP: rs397516761
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
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000037478 SCV000061136 uncertain significance not specified 2014-07-03 criteria provided, single submitter clinical testing The Glu1147fs variant in MYH6 has not been reported in any other families with c ardiomyopathy. Data from large population studies is insufficient to assess its frequency in the general population. This variant is predicted to cause a frames hift, which alters the protein?s amino acid sequence beginning at position 1147 and lead to a premature termination codon 86 amino acids downstream. This altera tion is then predicted to lead to a truncated or absent protein. Variants in MYH 6 have been reported in both individuals with in HCM and DCM (Carniel 2005, Hers hberger 2010), though its role in disease not yet well defined and it is unclear if a heterozygous loss-of-function variant would play a role in disease. In sum mary, the clinical significance of the Glu1147fs variant is uncertain.
Eurofins Ntd Llc (ga) RCV000732681 SCV000860660 uncertain significance not provided 2018-03-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV003298067 SCV003997308 uncertain significance Cardiovascular phenotype 2023-04-03 criteria provided, single submitter clinical testing The c.3437dupA variant, located in coding exon 24 of the MYH6 gene, results from a duplication of A at nucleotide position 3437, causing a translational frameshift with a predicted alternate stop codon (p.E1147Gfs*86). This alteration is expected to result in protein truncation or nonsense-mediated mRNA decay. However, loss of function of MYH6 has not been established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003514306 SCV004321026 uncertain significance Hypertrophic cardiomyopathy 14 2023-09-08 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 44485). This variant has not been reported in the literature in individuals affected with MYH6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu1147Glyfs*86) in the MYH6 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in MYH6 cause disease.

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.