Extended Data Fig. 1: Predicted effect of homozygous NRAP variant in different transcripts.
From: Exploring the complex spectrum of dominance and recessiveness in genetic cardiomyopathies
The homozygous NRAP variant GRCh37:chr10-115391614-A-G was detected in one individual in the cohort of 3222 British adults of Pakistani heritage by Narasimhan et al.14 (highlighted in red). The variant affects a splice donor site in two transcripts (ENST00000360478:c.1635+2 T > C / ENST00000359988:c.1740+2 T > C) but acts as missense variant in two others (ENST00000369360:p.Val546Ala / ENST00000369358:p.Val581 Ala). This is due to differential splicing of 24 bases (underlined) in the intron between exons 16 and 17. Therefore, although annotated as a potential loss-of-function variant, its effect is expected to be much less severe than most truncating variants in NRAP due to the milder missense variant effect in two of the NRAP transcripts.
