ClinVar Miner

Submissions for variant NM_000329.3(RPE65):c.1451G>A (p.Gly484Asp) (rs62653015)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000085175 SCV000565496 likely pathogenic not provided 2016-08-16 criteria provided, single submitter clinical testing The G484D variant has been reported previously in association with autosomal recessive retinitis pigmentosa (Stone et al., 2003) and in another individual with Severe Early Childhood Onset Retinal Dystrophy (SECORD) presenting with a remarkable preservation of vision with adequate lighting and white retinal dots that were seen to fade with time and were replaced by RPE changes (Weleber et al., 2011). The G484D 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 G484D 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. One other variant in a nearby residue (D477G) has been reported in the Human Gene Mutation Database in association with and RPE65-related disorder (Stenson et al., 2014). Therefore, based on the currently available information, G484D is a likely pathogenic variant.
Retina International RCV000085175 SCV000117312 not provided not provided no assertion provided not provided
Laboratory of Genetics in Ophthalmology,Institut Imagine RCV001250703 SCV001425578 likely pathogenic Leber congenital amaurosis 2 no assertion criteria provided research

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