rs11570112

rs11570112, also known as c.2992C>T, p.Gln998Ter and Q998X, represents a rare mutation in the MYBPC3 gene on chromosome 11. For multiple reasons discussed below, interpretation of the impact of this SNP is highly problematic. In addition to the reporting discrepancies between two different DTC labs (AncestryDNA and 23andMe) discussed below, the ClinVar record is decidedly mixed about whether this is, or is not, a pathogenic mutation for hypertrophic cardiomyopathy. After initially being classified of uncertain significance in 2011 by LabCorp, it was classified as benign in 2013 by both an NIH lab and by GeneDx, but in 2014, GeneDx re-classified it as pathogenic. Furthermore, in a dissertation published in July 2015 for a Masters in Genetic Counseling scholarworks.csustan.ede, rs11570112 was discussed in depth as a variant with conflicting interpretation between ClinVar and labs in the SHaRe academic consortium specializing in cardiomyopathy diagnosis theshareregistry.org, citing one group as saying it was benign and the other of uncertain significance. AncestryDNA seems to report the common genotype for this SNP on OpenSNP as C,C on the plus strand, which shows up as G,G on the minus strand in Promethease. 23andme seems to report the common genotype for this SNP as GG on the plus strand, which shows up as C,C on the minus strand on Promethease. This is an ambiguous flip (C/G). Th first 10 or so C,C checked on OpenSNP were all AncestyDNA reports, and given the extremely low frequency of the pathogenic allele, this is most likely an ambiguous flip problem. AncestryDNA users with a homozygous "pathogenic" GG reported by Promethease seem more likely to be wild type. Additionally, both C,C and G,G are far more common on OpenSNP than C,G, which deviates from Hardy-Weinberg. Additionally, newer 23andme (v4) microarrays do not seem to report any data for this SNP at all.

C;G

see discussion at rs11570112

C;C

see discussion at rs11570112