Description
The MYBPC3 Arg1022His is a rare variant and is present in the 1000 genomes project (MAF=0.0002; http://www.1000genomes.org/), and absent in the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/). We identified this variant in 1 HCM proband of Indian descent, who was heterozygous for MYBPC3 Arg1022His, and also carries another variant (LDB3 Gln97Arg) of "uncertain significance". The proband has no family history of disease or SCD. Interestingly, different rare variants at this position (Arg1022Cys, Arg1022Pro, Arg1022Ser) have also been reported in multiple HCM individuals, suggesting that an amino acid substitution at this site may not be tolerated. Computational tools SIFT, MutationTaster, and PolyPhen-2 predict this variant to have a deleterious effect, but no prediction is called by PolyPhen-HCM. In summary, based on rarity in the general population and our limited familial data, we have classified MYBPC3 Arg1022His as a variant of "uncertain significance". Further evidence is required to fully understand its pathogenic role in HCM.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | germline | yes | not provided | not provided | not provided | | not provided | not provided | 1 | not provided |
