ClinVar

Description

TheABCA4 c.203C>G (p.Pro68Arg) missense variant has been reported in three studies in which it is identified in four individuals, including a sibling pair, with recessively inherited Stargardt disease, all in a compound heterozygous state with a second missense variant (Shroyer et al. 2000; Cideciyan et al. 2012; Schulz et al. 2017). The mother of the affected siblings was diagnosed with age-related macular degeneration and carried the p.Pro68Arg variant in a heterozygous state (Shroyer et al. 2000). The variant was absent from 440 control chromosomes (Lewis et al. 1999) and is reported at a frequency of 0.00007 in the European (non-Finnish) population of the Genome Aggregation Database, but this is based on one allele so the variant is presumed to be rare. Another missense variant at the same amino acid position (p.Pro68Leu) has also been seen in individuals with ABCA4-related conditions, including at least one individual with Stargardt disease who carried the variant in a compound heterozygous state (Rivera et al. 2000). Based on the collective evidence, the p.Pro68Arg variant is classified as likely pathogenic for ABCA4-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.