ClinVar

Description

The p.R101H variant (also known as c.302G>A), located in coding exon 2 of the PKP2 gene, results from a G to A substitution at nucleotide position 302. The arginine at codon 101 is replaced by histidine, an amino acid with highly similar properties. This variant has been reported in individuals with Brugada syndrome, hypertrophic cardiomyopathy, and dilated cardiomyopathy, although many also carried variants in other cardiac-related genes (Pugh TJ et al. Genet Med. 2014;16(8):601-8; Lopes LR et al. J Med Genet, 2013 Apr;50:228-39; Allegue C et al. PLoS ONE. 2015;10(7):e0133037). In addition, this variant was reported in an individual with arrhythmogenic right ventricular cardiomyopathy who was also homozygous for a DSG2 pathogenic mutation (Fressart V et al. Europace. 2010;12(6):861-8). This variant has also been reported as a secondary cardiac variant of unknown significance in an exome cohort (Ng D et al. Circ Cardiovasc Genet. 2013;6(4):337-46). This amino acid position is not well conserved in available vertebrate species, and histidine is the reference amino acid in one species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.