Description
The c.3628-41_3628-17del25 variant in the MYBPC3 gene has been previously reported in the heterozygous, compound heterozygous, or homozygous state in >30 unrelated individuals with cardiomyopathy (Alfares et al., 2015; Bashyam et al., 2012; Dhandapany et al., 2009; Waldmuller et al., 2003). The c.3628-41_3628-17del25 variant has also been identified in 981/30,592 South Asian chromosomes, including 19 homozygotes, by the Genome Aggregation Database (http://gnomad.broadinstitute.org/), indicating it may be a common, reduced penetrance allele in this population. While the c.3628-41_3628-17del25 variant is relatively common in individuals of South Asian ancestry, case-control studies have found an associated risk with cardiomyopathy (Dhandapany et al., 2009). This variant is predicted to disrupt splicing and lead to skipping of exon 33, reducing the length of the protein (Dhandapany et al., 2009; Waldmuller et al., 2003). These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, there is sufficient evidence to classify the c.3628-41_3628- 17del25 variant as likely pathogenic with reduced penetrance for hypertrophic cardiomyopathy in an autosomal dominant manner based on the information above. [ACMG evidence codes used: PS4; PM4]
| # | 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 | not provided | not provided |
