ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.3642G>A (p.Trp1214Ter) (rs368765949)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CSER _CC_NCGL, University of Washington RCV000206843 SCV000196741 likely pathogenic Hypertrophic cardiomyopathy 2014-06-01 criteria provided, single submitter research
GeneDx RCV000158241 SCV000208176 pathogenic not provided 2017-01-26 criteria provided, single submitter clinical testing The W1214X variant in the MYBPC3 gene has been reported in an Indian male patient with familial HCM who also harbored another variant in the MYH7 gene (Bashyam M et al., 2012). The variant was absent from 100 ethnically matched control individuals. W1214X is predicted to cause loss of normal protein function either by protein truncation or nonsense mediated mRNA decay. Other nonsense variants in the MYBPC3 gene have been reported in association with HCM. In summary, W1214X in the MYBPC3 gene is interpreted as a disease-causing variant.
Laboratory of Genetics and Molecular Cardiology, University of São Paulo RCV000201437 SCV000256182 likely pathogenic Familial hypertrophic cardiomyopathy 4 criteria provided, single submitter clinical testing
Invitae RCV000206843 SCV000259243 pathogenic Hypertrophic cardiomyopathy 2018-12-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp1214*) in the MYBPC3 gene. It is expected to result in an absent or disrupted protein product. A different variant (c.3641G>A) giving rise to the same protein effect observed here (p.Trp1214*) has been reported in several individuals affected with hypertrophic cardiomyopathy (PMID: 21959974, 24093860), indicating that this residue may be critical for protein function. ClinVar contains an entry for this variant (Variation ID: 31800536). Loss-of-function variants in MYBPC3 are known to be pathogenic (PMID: 19574547). For these reasons, this variant has been classified as Pathogenic.
Color RCV001179298 SCV001343928 pathogenic Cardiomyopathy 2019-08-20 criteria provided, single submitter clinical testing
Petrovsky National Research Centre of Surgery, The Federal Agency for Scientific Organizations RCV001263457 SCV001441524 likely pathogenic Primary dilated cardiomyopathy; Left ventricular noncompaction cardiomyopathy 2020-10-15 criteria provided, single submitter clinical testing We observed a c.3642G>A (p.W1214*) genetic variant in a 30-y.o. female proband, diagnosed with non-compaction cardiomyopathy, dilatation of cardiac chambers and heart rhythm disturbances. The proband also carried the additional variant of unknown clinical significance in MYBPC3 gene - p.P186L in heterozygous state. The family was unavailable for screening. The p.W1214* genetic variant is a nonsense mutation in the MYBPC3 gene. No functional studies are available for the p.W1214* variant, however, nonsense variants in MYBPC3 gene are well-known to cause cardiomyopathy through haploinsufficiency. According to Cardio Classifier predictions, mRNA carrying the p.W1214* variant, will be processed through nonsence-mediated decay mechanism, leading to haploinsufficiency. We assume that the p.W1214* variant could be classified as likely pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000158241 SCV001447398 pathogenic not provided 2020-10-23 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.