Submissions for variant NM_000350.3(ABCA4):c.2609C>T (p.Pro870Leu) (rs746566873)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Human Genetics, Univ. Regensburg,Univ. Regensburg	RCV000408530	SCV000281850	likely pathogenic	Stargardt disease 1	2016-01-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000490201	SCV000577641	likely pathogenic	not provided	2015-08-20	criteria provided, single submitter	clinical testing	The P870L variant has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The P870L 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. The P870L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. 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 variant in this residue and missense variant in nearby residues (P870S, P862L, G863A, F873L) have been reported in the Human Gene Mutation Database in association with ABCA4-related disorders (Stenson et al., 2014). Therefore, this variant is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded.