ClinVar Miner

Submissions for variant NM_152443.3(RDH12):c.506G>A (p.Arg169Gln)

gnomAD frequency: 0.00001  dbSNP: rs971610277
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Diagnostics Laboratory, M Health Fairview: University of Minnesota RCV000761341 SCV000891327 likely pathogenic Leber congenital amaurosis 13 2016-10-13 criteria provided, single submitter clinical testing
Invitae RCV000761341 SCV001213448 pathogenic Leber congenital amaurosis 13 2023-12-09 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 169 of the RDH12 protein (p.Arg169Gln). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individuals with autosomal recessive Leber congenital amaurosis (PMID: 22065924, 25133751). ClinVar contains an entry for this variant (Variation ID: 623219). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RDH12 protein function with a positive predictive value of 80%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant disrupts the p.Arg169 amino acid residue in RDH12. Other variant(s) that disrupt this residue have been observed in individuals with RDH12-related conditions (PMID: 22065924, 26047050), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001073859 SCV001239423 pathogenic Retinal dystrophy 2018-07-13 criteria provided, single submitter clinical testing
GeneDx RCV001530599 SCV001745482 likely pathogenic not provided 2021-06-23 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 22065924, 25133751, 24705292, 32172635, 27535533, 28559085, 30134391)
Fulgent Genetics, Fulgent Genetics RCV000761341 SCV002794784 pathogenic Leber congenital amaurosis 13 2022-03-26 criteria provided, single submitter clinical testing
Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital RCV001530599 SCV002818221 pathogenic not provided 2022-12-17 criteria provided, single submitter clinical testing
Baylor Genetics RCV000761341 SCV004208586 pathogenic Leber congenital amaurosis 13 2023-08-29 criteria provided, single submitter clinical testing
Ocular Genomics Institute, Massachusetts Eye and Ear RCV000761341 SCV001146944 likely pathogenic Leber congenital amaurosis 13 2019-08-01 no assertion criteria provided clinical testing

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