ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.2785G>A (p.Glu929Lys) (rs730880161)

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
Blueprint Genetics RCV000157362 SCV000207100 likely pathogenic Primary familial hypertrophic cardiomyopathy 2015-06-16 criteria provided, single submitter clinical testing
GeneDx RCV000225718 SCV000208788 likely pathogenic not provided 2018-12-18 criteria provided, single submitter clinical testing This mutation is denoted Glu929Lys (aka E929K) at the protein level and c.2785 G>A at the cDNA level. The Glu929Lys mutation has not been previously reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Glu929Lys represents a non-conservative amino acid substitution of a negatively charged Glutamic acid residue with a positively charged Lysine at a residue that is conserved across species throughout evolution. In silico analysis (PolyPhen2) predicts Glu929Lys is probably damaging to the protein structure/function. Furthermore, mutations in neighboring codons (Glu927Lys, Asp928Asn, Glu930Gln, Glu930Lys) have been reported in association with HCM, further supporting the functional importance of this region of the protein. Moreover, Glu929Lys was not detected in up to 400 alleles from control individuals of Caucasian ancestry nor in up to 200 alleles of African American ancestry tested at GeneDx. Similarly, according to the NHLBI ESP Exome Variant Server, Glu929Lys was not observed in at approximately 5,300 individuals from European and African American backgrounds, indicating that it is not a common sequence variant in these populations. Glu929Lys has also been identified multiple other unrelated individuals tested for HCM at GeneDx. The variant is found in HCM panel(s).

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.