Have questions? Visit https://www.reddit.com/r/SNPedia

rs11570112

From SNPedia

Orientationminus
Stabilizedminus
Geno Mag Summary
(C;C) 0 common in clinvar
(C;G) 1 interpretation problematic vis-a-vis cardiomyopathy for several reasons
(G;G) 0.5 miscalled by AncestryDNA; interpretation problematic anyway
ReferenceGRCh38.p2 38.2/144
Chromosome11
Position47333924
GeneMYBPC3
is asnp
is mentioned by
dbSNPrs11570112
ebirs11570112
HLIrs11570112
Exacrs11570112
Varsomers11570112
Maprs11570112
PheGenIrs11570112
hapmaprs11570112
1000 genomesrs11570112
hgdprs11570112
ensemblrs11570112
gopubmedrs11570112
geneviewrs11570112
scholarrs11570112
googlers11570112
pharmgkbrs11570112
gwascentralrs11570112
openSNPrs11570112
23andMers11570112
23andMe allrs11570112
SNP Nexus

SNPshotrs11570112
SNPdbers11570112
MSV3drs11570112
GWAS Ctlgrs11570112
Max Magnitude1

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 [1], rs11570112 was discussed in depth as a variant with conflicting interpretation between ClinVar and labs in the SHaRe academic consortium specializing in cardiomyopathy diagnosis [2], 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;C) (C;G) (G;G) 28
ClinVar
Risk rs11570112(G,T;G,T)
Alt rs11570112(G,T;G,T)
Reference rs11570112(C;C)
Significance Other
Disease not provided Primary dilated cardiomyopathy not specified Primary familial hypertrophic cardiomyopathy Hypertrophic cardiomyopathy
Variation info
Gene MYBPC3
CLNDBN not provided Primary dilated cardiomyopathy not specified Primary familial hypertrophic cardiomyopathy Hypertrophic cardiomyopathy
Reversed 1
HGVS NC_000011.9:g.47355475G>A; NC_000011.9:g.47355475G>C
CLNSRC
CLNACC RCV000158203.2, RCV000030288.1, RCV000035545.6, RCV000172828.1, RCV000205320.2,