ClinVar Miner

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

gnomAD frequency: 0.00004  dbSNP: rs61751395
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Total submissions: 7
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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 Severe early-childhood-onset retinal dystrophy 2016-01-01 criteria provided, single submitter clinical testing
GeneDx RCV000085471 SCV000511885 pathogenic not provided 2021-12-08 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect (severe reduction in protein expression) (Shroyer et al., 2001); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 12442277, 15942264, 21911583, 22229821, 15494742, 15192030, 11328725, 10711710, 17325136, 22661472, 24713488, 23096905, 25097154, 20696155, 31589614, 32619608, 29925512, 28559085, 29555955, 11687513)
Invitae RCV000085471 SCV001227097 pathogenic not provided 2023-12-06 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 767 of the ABCA4 protein (p.Val767Asp). This variant is present in population databases (rs61751395, gnomAD 0.004%). This missense change has been observed in individuals with Stargardt disease, retinitis pigmentosa or generalized choriocapillaris dystrophy (PMID: 10711710, 11687513, 24713488, 28559085, 29555955, 29925512). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 99127). 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 ABCA4 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects ABCA4 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 Center for Human Genetics Tuebingen RCV000085471 SCV001245779 pathogenic not provided 2016-11-01 criteria provided, single submitter clinical testing
MGZ Medical Genetics Center RCV000408526 SCV002580049 likely pathogenic Severe early-childhood-onset retinal dystrophy 2022-06-01 criteria provided, single submitter clinical testing
Retina International RCV000085471 SCV000117608 not provided not provided no assertion provided not provided

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