ClinVar Miner

Submissions for variant NM_000329.3(RPE65):c.118G>A (p.Gly40Ser) (rs61751281)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Ophthalmology and Visual Sciences Kyoto University RCV000132582 SCV000172525 pathogenic Retinitis pigmentosa no assertion criteria provided not provided Converted during submission to Pathogenic.
GeneDx RCV000085155 SCV000329701 pathogenic not provided 2016-08-12 criteria provided, single submitter clinical testing The G40S variant in the RPE65 gene has been reported previously, in the homozygous or compound heterozygous state, in unrelated individuals with Leber congenital amaurosis (Morimura et al.,1998; Galvin et al., 2005; Jacobson et al., 2009; Pasadhika et al., 2010; Ripamonti et al., 2014). The G40S variant was not observed in approximately 6500 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 G40S 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 vitro functional studies demonstrated that the G40S variant results in a significant reduction in isomerization acitivity and significant reduction in protein expression (Redmond et al., 2005; Li et al., 2014). Therefore, we interpret G40S as a pathogenic variant.
Retina International RCV000085155 SCV000117292 not provided not provided no assertion provided not provided

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