Submissions for variant NM_000350.3(ABCA4):c.3389T>C (p.Ile1130Thr) (rs1064793010)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000485764	SCV000564530	likely pathogenic	not provided	2014-05-27	criteria provided, single submitter	clinical testing	A novel I1130T variant that is likely pathogenic was identified in theABCA4 gene. It has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The I1130T variant was not observed in approximately 6,500 individuals of European and African American ancestry in an external variant database, indicating it is not a common benign variant in these populations. The 1130T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other 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. Missense variants in nearby residues (G1127E, R1129C, R1129H and I1133T) have been reported in the Human Gene Mutation Database in association with Stargardt disease, age-related macular degeneration, and retinal disease (Stenson et al., 2009), supporting the functional importance of this region of the protein. Therefore, this variant is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded.