ClinVar

Description

ThThe p.Y681C variant (also known as c.2042A>G), located in coding exon 9 of the RBM20 gene, results from an A to G substitution at nucleotide position 2042. The tyrosine at codon 681 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported in a sudden infant death cohort and in a dilated cardiomyopathy (DCM) cohort; however, clinical details were limited (Santori M et al. Arch Dis Child. 2015;100:952-6; van den Hoogenhof MMG. Circulation. 2018;138:1330-1342). This variant has also been detected in a pediatric DCM cohort where, in one individual, it co-occurred with a variant in another cardiomyopathy-related gene (Herkert JC et al. Genet. Med., 2018 11;20:1374-1386). This variant was also detected in a cardiomyopathy/arrhythmia genetic testing cohort; however, clinical details were limited, and additional cardiac variants were detected in some cases (van Lint FHM et al. Neth Heart J, 2019 Jun;27:304-309). This variant has also been reported in an arrhythmogenic disorders cohort (Marschall C et al. Cardiovasc Diagn Ther, 2019 Oct;9:S292-S298). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.