ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.2300T>A (p.Val767Asp) (rs61751395)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, Univ. Regensburg,Univ. Regensburg RCV000408526 SCV000281844 pathogenic Stargardt disease 1 2016-01-01 criteria provided, single submitter clinical testing
GeneDx RCV000085471 SCV000511885 likely pathogenic not provided 2016-02-01 criteria provided, single submitter clinical testing The V767D variant has been reported in association with ABCA4-related disorders (Bertelsen et al., 2014; Klevering et al., 2004; Stenirri et al., 2004; Duno et al., 2012; Zernant et al., 2011). In vitro functional studies demonstrated that the presence of the V767D variant results in severely reduce ABCR protein expression (Shroyer et al., 2001). The V767D 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 V767D 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 is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. This variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Invitae RCV000085471 SCV001227097 pathogenic not provided 2020-01-07 criteria provided, single submitter clinical testing This sequence change replaces valine with aspartic acid at codon 767 of the ABCA4 protein (p.Val767Asp). The valine residue is highly conserved and there is a large physicochemical difference between valine and aspartic acid. This variant is present in population databases (rs61751395, ExAC 0.002%). This variant has been observed in individual(s) with Stargardt disease, retinitis pigmentosa or generalized choriocapillaris dystrophy (PMID: 10711710, 29925512, 28559085, 11687513, 29555955, 24713488). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 99127). This variant has been reported to affect ABCA4 protein function (PMID: 11687513). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001074642 SCV001240234 pathogenic Retinal dystrophy 2019-02-06 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000085471 SCV001245779 pathogenic not provided 2016-11-01 criteria provided, single submitter clinical testing
Retina International RCV000085471 SCV000117608 not provided not provided no assertion provided not provided

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