rs79023478

rs79023478, also known as c.13031G>A, p.Arg4344Gln and R4344Q, represents a variant in the obscurin OBSCN gene on chromosome 1. A 2007 report of a 19-year old Japanese hypertrophic cardiomyopathy patient carrying one rs79023478(A) allele concluded, following in vitro functional studies, that this allele was likely to be causative for the condition. A 2017 report based on studying mice genetically engineered to be homozygous for the rs79023478(A) variant concluded that under sedentary conditions, the R4344Q mutation results in Ca2+ deregulation and spontaneous arrhythmia, whereas in the presence of chronic, pathological stress, it leads to cardiac remodeling and dilation. Note however that this study did not study mice heterozygous for the rs79023478(A) variant. Furthermore, a 2016 publication studying hypertrophic cardiomyopathy diagnoses across diverse populations observed that there is a very large difference in the frequency of the R4344Q variant between Caucasians and African-Americans: around 0% vs 10%, respectively. Given a hypertrophic cardiomyopathy frequency of about 1 in 500 people in general across most populations (including African-Americans), this argues that either the penetrance of the R4344Q variant is very low or even that it is benign, although perhaps it might play a (minor?) role in the development of cardiovascular disease in a more general way and/or in the presence of certain environmental or biological stressors.

A;A

see discussion at rs79023478

A;G

see discussion at rs79023478