ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.1529T>C (p.Leu510Pro)

gnomAD frequency: 0.00001  dbSNP: rs886039299
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000256040 SCV000321337 likely pathogenic not provided 2022-01-24 criteria provided, single submitter clinical testing 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: 29925512, 28005406)
Labcorp Genetics (formerly Invitae), Labcorp RCV000256040 SCV001589692 pathogenic not provided 2024-04-01 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 510 of the ABCA4 protein (p.Leu510Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Stargardt disease or cone-rod dystrophy (PMID: 29925512; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 265011). 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.Leu510 amino acid residue in ABCA4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22229821, 24713488, 30718709). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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