Description
A R216H variant that is likely pathogenic was identified in the LMNA gene. It has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The R216H variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. A missense mutation in this same residue (R216C) and in nearby residues (I210S, L215P, K219T, K219N) have been reported in association with cardiomyopathy, supporting the functional importance of this region of the protein. However, the R216H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in DCM-CRDM panel(s).
# | Sample | Method | Observation |
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Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
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1 | germline | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |