ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.2965G>A (p.Val989Ile)

gnomAD frequency: 0.00001  dbSNP: rs552307838
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001099944 SCV001256437 uncertain significance ABCA4-Related Disorders 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae RCV001203658 SCV001374832 uncertain significance not provided 2022-10-24 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 989 of the ABCA4 protein (p.Val989Ile). This variant is present in population databases (rs552307838, gnomAD 0.04%). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 29641573). ClinVar contains an entry for this variant (Variation ID: 875783). 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 not expected to disrupt ABCA4 protein function. This variant disrupts the p.Val989 amino acid residue in ABCA4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22247458, 23755871, 25066811, 28327576; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV001203658 SCV001988334 uncertain significance not provided 2019-03-26 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Identified with a second ABCA4 variant in a patient with retinitis pigmentosa in published literature (Huang et al., 2018).; This variant is associated with the following publications: (PMID: 29641573)

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