ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.2291G>A (p.Cys764Tyr)

gnomAD frequency: 0.00001  dbSNP: rs61749428
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg RCV000408455 SCV000281843 likely pathogenic Severe early-childhood-onset retinal dystrophy 2016-01-01 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001074411 SCV001239993 pathogenic Retinal dystrophy 2019-08-11 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000085467 SCV001245780 pathogenic not provided 2017-12-01 criteria provided, single submitter clinical testing
Institute of Medical Molecular Genetics, University of Zurich RCV000408455 SCV001548049 likely pathogenic Severe early-childhood-onset retinal dystrophy 2021-01-30 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000085467 SCV003522774 pathogenic not provided 2023-12-12 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 764 of the ABCA4 protein (p.Cys764Tyr). This variant is present in population databases (rs61749428, gnomAD 0.007%). This missense change has been observed in individual(s) with autosomal recessive Stargardt disease (PMID: 10958763, 28118664, 33546218). ClinVar contains an entry for this variant (Variation ID: 99123). 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%. For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg RCV001074411 SCV005070172 likely pathogenic Retinal dystrophy 2020-01-01 criteria provided, single submitter clinical testing
GeneDx RCV000085467 SCV005201551 likely pathogenic not provided 2024-01-29 criteria provided, single submitter clinical testing Published functional studies suggest this variant results in mild impairment of ABCA4 expression and functional properties, however additional studies are needed to validate the functional effect of this variant (PMID: 33375396); Not observed at significant frequency in large population cohorts (gnomAD); 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: 10958763, 31964843, 28118664, 32531858, 33546218, 33375396)
Retina International RCV000085467 SCV000117604 not provided not provided no assertion provided not provided

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