ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.3292C>T (p.Arg1098Cys) (rs756840095)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, Univ. Regensburg,Univ. Regensburg RCV000408518 SCV000281864 likely pathogenic Stargardt disease 1 2016-01-01 criteria provided, single submitter clinical testing
GeneDx RCV000478178 SCV000564528 likely pathogenic not provided 2016-02-23 criteria provided, single submitter clinical testing While the R1098C variant has been reported previously in association with an ABCA4 related disorder (Rosenberg et al., 2007; Cideciyan et al., 2009; Passerini et al., 2010; Rivera et al., 2000), Passerini et al., reports that R1098C was located on the same allele in cis" with another pathogenic missense variant and on the opposite allele in "trans" with a third pathogenic variant. It is very rare for two pathogenic variants to be present on the same allele in one individual. This causes us to question if both R1098C and the other missense variant are indeed both pathogenic. The R1098C 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 R1098C 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. Therefore, based on the currently available information, R1098C is a strong candidate for a pathogenic variant."
Blueprint Genetics RCV001074682 SCV001240275 pathogenic Retinal dystrophy 2019-03-21 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001196593 SCV001367201 likely pathogenic Macular degeneration; Reduced visual acuity 2020-02-04 criteria provided, single submitter clinical testing This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2,PP3. This variant was detected in homozygous state.

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