ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.3323G>A (p.Arg1108His)

gnomAD frequency: 0.00003  dbSNP: rs61750121
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000085570 SCV001214614 pathogenic not provided 2023-12-19 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1108 of the ABCA4 protein (p.Arg1108His). This variant is present in population databases (rs61750121, gnomAD 0.004%). This missense change has been observed in individual(s) with Stargardt disease (PMID: 11328725, 28559085, 29925512). 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: 99219). 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.Arg1108 amino acid residue in ABCA4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16703556, 19074458, 26092729, 28559085). 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.
Blueprint Genetics RCV001073697 SCV001239256 pathogenic Retinal dystrophy 2017-04-12 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000085570 SCV001249464 pathogenic not provided 2020-05-01 criteria provided, single submitter clinical testing
Retina International RCV000085570 SCV000117708 not provided not provided no assertion provided not provided

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