ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.2947A>G (p.Thr983Ala)

dbSNP: rs1368508052
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001040117 SCV001203676 pathogenic not provided 2023-12-30 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 983 of the ABCA4 protein (p.Thr983Ala). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individuals with clinical features of ABCA4-related inherited retinal dystrophies (PMID: 25066811, 25444351, 30029497). ClinVar contains an entry for this variant (Variation ID: 838547). 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: 29145636). This variant disrupts the p.Thr983 amino acid residue in ABCA4. Other variant(s) that disrupt this residue have been observed in individuals with ABCA4-related conditions (PMID: 29925512), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Molecular Genetics, University of Zurich RCV001352962 SCV001548034 likely pathogenic Severe early-childhood-onset retinal dystrophy 2021-01-30 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV001040117 SCV001740217 likely pathogenic not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001040117 SCV001952030 likely pathogenic not provided no assertion criteria provided clinical testing

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