ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.1958G>A (p.Arg653His) (rs141823837)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484928 SCV000564521 likely pathogenic not provided 2014-06-19 criteria provided, single submitter clinical testing A novel R653H variant that is likely pathogenic was identified in the ABCA4 gene. The R653H variant has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The R653H variant was not observed at any significant frequency in approximately 6,500 individuals of European and African American ancestry in an external database.The R653H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar 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. Another missense variant at the same residue (R653C) has been reported in the Human Gene Mutation Database in association with Stargardt 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.

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