ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.6320G>A (p.Arg2107His) (rs62642564)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000085807 SCV000230703 uncertain significance not provided 2015-06-02 criteria provided, single submitter clinical testing
GeneDx RCV000085807 SCV000321358 pathogenic not provided 2018-12-12 criteria provided, single submitter clinical testing The R2107H variant in the ABCA4 gene has been reported previously in multiple unrelated individuals with Stargardt disease who also harbored a second ABCA4 pathogenic variant (Duncker et al., 2015; Lee et al., 2015; Kellner et al., 2009; Fujinami et al., 2013), suggesting that compound heterozygosity for R2107H and another pathogenic ABCA4 variant results in a phenotype consistent with the spectrum of ABCA4-related disorders. This variant is observed in 488/24024 (2.06%) alleles in individuals of African descent in large population cohorts (Lek et al., 2016). Consistent with this high carrier frequency, R2107H is reported to represent 19.3% of disease-associated alleles in Stargardt patients of African descent (Zernant et al., 2014). Although this variant has been reported in the homozygous state in individuals with Stargardt disease (Zernant et al., 2014; Shroyer et al., 2001), this variant has also been observed in the homozygous state in 5 individuals in large population cohorts (Lek et al., 2016), raising the possibility that homozygosity for R2107H may not associate with disease. The R2107H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, in-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Additionally, missense variants in the same codon (R2107C and R2107P) and in nearby residues (D2102E, R2106C) have been reported in the Human Gene Mutation Database in association with Stargardt disease (Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret R2107H as a pathogenic variant; however, additional genotype/phenotype studies are needed to better establish its contribution to disease.
Illumina Clinical Services Laboratory,Illumina RCV000391460 SCV000359203 likely benign Macular degeneration 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000291062 SCV000359204 likely benign Retinitis Pigmentosa, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000345905 SCV000359205 likely benign Cone-Rod Dystrophy, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000391457 SCV000359206 likely benign Stargardt Disease, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Institute of Human Genetics, Univ. Regensburg,Univ. Regensburg RCV000408534 SCV000281956 likely pathogenic Stargardt disease 1 2016-01-01 criteria provided, single submitter clinical testing
NEI Ophthalmic Genomics Laboratory,National Institutes of Health RCV000085807 SCV000119181 not provided not provided no assertion provided not provided
NIHR Bioresource Rare Diseases, University of Cambridge RCV000408534 SCV000599013 likely pathogenic Stargardt disease 1 2015-01-01 no assertion criteria provided research
NIHR Bioresource Rare Diseases, University of Cambridge RCV000505080 SCV000599014 likely pathogenic Macular dystrophy 2015-01-01 no assertion criteria provided research
Retina International RCV000085807 SCV000117950 not provided not provided no assertion provided not provided

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