ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.2966T>C (p.Val989Ala)

gnomAD frequency: 0.00089  dbSNP: rs61749454
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000085529 SCV000321347 pathogenic not provided 2023-07-04 criteria provided, single submitter clinical testing 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: 15161829, 22863181, 19406377, 32531858, 11328725, 14517951, 25066811, 16123440, 12397427, 11527935, 29126757, 29925512, 24550365, 28327576, 31980526, 32581362, 35119454, 35076026)
Invitae RCV000085529 SCV001202798 pathogenic not provided 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 989 of the ABCA4 protein (p.Val989Ala). This variant is present in population databases (rs61749454, gnomAD 0.3%). This missense change has been observed in individual(s) with ABCA4-related retinal disease (PMID: 22247458, 23755871, 25066811, 28327576; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 99180). 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.Val989 amino acid residue in ABCA4. Other variant(s) that disrupt this residue have been observed in individuals with ABCA4-related conditions (PMID: 29641573), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV001074424 SCV001240007 pathogenic Retinal dystrophy 2019-08-16 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000085529 SCV001249472 pathogenic not provided 2018-09-01 criteria provided, single submitter clinical testing
Retina International RCV000085529 SCV000117666 not provided not provided no assertion provided not provided
Eurofins Ntd Llc (ga) RCV000085529 SCV000339698 uncertain significance not provided 2016-02-22 flagged submission clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504904 SCV000598956 likely pathogenic Severe early-childhood-onset retinal dystrophy 2015-01-01 no assertion criteria provided research

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.