ClinVar Miner

Submissions for variant NM_000329.3(RPE65):c.394G>A (p.Ala132Thr) (rs61752878)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483376 SCV000565494 uncertain significance not specified 2016-06-29 criteria provided, single submitter clinical testing The A132T variant in the RPE65 gene was identified in the homozygous state through direct sequencing of the RPE65 gene in two siblings with autosomal recessive retinitis pigmentosa (arRP) (Morimura et al., 1998). The A132T variant has also been reported in the heterozygous state in a few unrelated individuals with arRP where no second RPE65 variant was identified (Thompson et al., 2000; Bereta et al., 2008). The A132T variant was observed with a frequency of 1.28% (206/16510 alleles) in individuals of South Asian background in the Exome Aggregation Consortium (ExAC) data set, including 4 homozygotes, indicating this may be a rare (benign) variant in this population (Lek et al., 2016). The A132T 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 in mammals. Functional studies indicate the A132T variant results in a 50% reduction of isomerization activity; however the residual isomerization activity associated with this variant was higher than most reported RPE65 pathogenic variants (Redmond et al., 2005). Given the available data, we interpret A132T as a variant of uncertain significance.
Counsyl RCV000665910 SCV000790116 likely benign Leber congenital amaurosis 2; Retinitis pigmentosa 20 2017-03-06 criteria provided, single submitter clinical testing
Invitae RCV000665910 SCV001091443 benign Leber congenital amaurosis 2; Retinitis pigmentosa 20 2019-12-31 criteria provided, single submitter clinical testing
Mendelics RCV000986331 SCV001135304 uncertain significance Leber congenital amaurosis 2 2019-05-28 criteria provided, single submitter clinical testing
OMIM RCV000013998 SCV000034245 uncertain significance Retinitis pigmentosa 20 1998-03-17 no assertion criteria provided literature only
Retina International RCV000085196 SCV000117333 not provided not provided no assertion provided not provided

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