ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.5383T>G (p.Leu1795Val)

gnomAD frequency: 0.00001  dbSNP: rs1188515677
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001040976 SCV001204570 likely pathogenic not provided 2023-11-14 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1795 of the ABCA4 protein (p.Leu1795Val). This variant is present in population databases (no rsID available, gnomAD 0.006%). This missense change has been observed in individual(s) with cone-rod dystrophy (PMID: 30902645). ClinVar contains an entry for this variant (Variation ID: 839263). 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%. This variant disrupts the p.Leu1795 amino acid residue in ABCA4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30060493, 32619608). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Department of Genetics, Fundacion Jimenez Diaz University Hospital RCV001270350 SCV001450575 uncertain significance Retinitis pigmentosa criteria provided, single submitter clinical testing This variant is present in population databases (rs1188515677, gnomAD_exomes 0.008%), predicted deleterious by in-silico pathogenicity predictors. (ACMG: PM2 Moderate; PP3 Supporting)
Fulgent Genetics, Fulgent Genetics RCV002479263 SCV002776537 uncertain significance Cone-rod dystrophy 3; Age related macular degeneration 2; Severe early-childhood-onset retinal dystrophy; Retinitis pigmentosa 19 2021-07-26 criteria provided, single submitter clinical testing

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