|| common in clinvar
|| risk genotype
|?|| (A;A) (A;G) (G;G) ||28|
is a nonsynonymous SNP in exon 25 of the MYH6
gene, coding for the alpha myosin heavy chain (alpha-MyHC) protein. The A->G nucleotide change results in the A1101V missense mutation in alpha-MyHc.
[rs365990]] was discovered in a study conducted by deCODE Genetics [PMID 20062063] as being most significantly associated primarily with heart rate, but also with PR interval. In the Icelandic cohort of ~10,000 individuals in the discovery phase and an additional ~10,000 individuals in the follow-up phase, the rs365990 G allele frequency was 0.34, and the G allele was associated with decreased heart rate (p=9.4E-11 for both phases combined) and with a prolonged PR interval (p=1.8E-5 combined). After adjusting for heart rate, the association of rs365990 with PR interval maintained significance (p=0.0027 combined).
rs365990[G] is associated with a 0.91-beat decrease in heart rate per minute [PMID ]. This was replicated in a meta-analysis of 38,991 individuals of European descent, where the A allele of rs452306 was found to be associated with with a 0.58bpm decrease in resting heart rate per A allele [PMID ]. rs452306 is in linkage disequilibrium with rs365990 (r2=0.96 in HapMap CEU), and it was suggested that rs365990 is the functional variant.
It was not, however, associated with atrial fibrillation (p=0.14 combined), pacemaker (p=0.13 combined), sick sinus syndrome (p=0.18 combined), or advanced AV block (p=0.33 combined).
[PMID 20592870] Comparison of the Illumina Genome Analyzer and Roche 454 GS FLX for resequencing of hypertrophic cardiomyopathy-associated genes.
[PMID 21378987] A rare variant in MYH6 is associated with high risk of sick sinus syndrome.
|| not reviewed
|| Insufficiently evaluated not reviewed
|| [PMID 23583979]
|| Heart rate
|| Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders.
| Risk Allele
| Odds Ratio
|| .56 [0.47-0.66] unit increase