ClinVar Miner

Submissions for variant NM_017534.6(MYH2):c.1975-1G>C

gnomAD frequency: 0.00001  dbSNP: rs201082272
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413648 SCV000490648 likely pathogenic not provided 2016-03-11 criteria provided, single submitter clinical testing The c.1975-1G>C variant in the MYH2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This splice site variant destroys the canonical splice acceptor site in intron 17. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.1975-1G>C variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.1975-1G>C as a likely pathogenic variant.
Invitae RCV001377614 SCV001574995 likely pathogenic Myopathy, proximal, and ophthalmoplegia 2023-05-19 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with MYH2-related conditions. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 372425). This variant is present in population databases (rs201082272, gnomAD 0.005%). This sequence change affects an acceptor splice site in intron 17 of the MYH2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MYH2 are known to be pathogenic (PMID: 20418530, 23388406, 24193343).
Revvity Omics, Revvity RCV001377614 SCV002017841 likely pathogenic Myopathy, proximal, and ophthalmoplegia 2019-07-29 criteria provided, single submitter clinical testing

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.