ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.6391G>A (p.Glu2131Lys)

gnomAD frequency: 0.00001  dbSNP: rs61750652
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV001074273 SCV001239846 likely pathogenic Retinal dystrophy 2019-05-15 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000085817 SCV003523290 pathogenic not provided 2025-01-26 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 2131 of the ABCA4 protein (p.Glu2131Lys). This variant is present in population databases (rs61750652, gnomAD 0.002%). This missense change has been observed in individual(s) with Stargardt disease (PMID: 9973280, 23143460, 30834176). 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: 99457). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt ABCA4 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004526616 SCV005039830 pathogenic Stargardt disease 2024-03-18 criteria provided, single submitter clinical testing Variant summary: ABCA4 c.6391G>A (p.Glu2131Lys) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251474 control chromosomes (gnomAD). c.6391G>A has been reported in the literature in multiple individuals affected with Stargardt Disease (e.g. Lewis_1999, Stone_2017). These data indicate that the variant is very likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 9973280, 28559085). ClinVar contains an entry for this variant (Variation ID: 99457). Based on the evidence outlined above, the variant was classified as pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005031590 SCV005656852 pathogenic Cone-rod dystrophy 3; Age related macular degeneration 2; Severe early-childhood-onset retinal dystrophy; Retinitis pigmentosa 19 2024-03-19 criteria provided, single submitter clinical testing
Retina International RCV000085817 SCV000117960 not provided not provided no assertion provided not provided

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.