ClinVar Miner

Submissions for variant NM_000350.3(ABCA4):c.3212C>T (p.Ser1071Leu)

gnomAD frequency: 0.00001  dbSNP: rs61750065
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
GeneDx RCV000085559 SCV000577305 pathogenic not provided 2023-07-11 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 15192030, 23341817, 26720470, 31589614, 35156991, 33301772, 9973280, 29555955)
Invitae RCV000085559 SCV001580409 pathogenic not provided 2023-05-12 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 99208). This missense change has been observed in individual(s) with ABCA4-related inherited retinal dystrophies (PMID: 9973280, 15192030, 26720470, 29555955; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs61750065, gnomAD 0.006%). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1071 of the ABCA4 protein (p.Ser1071Leu).
DASA RCV002255094 SCV002526422 pathogenic ABCA4-Related Disorders 2022-06-10 criteria provided, single submitter clinical testing The c.3212C>T;p.(Ser1071Leu) missense change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 99208; PMID: 29555955; PMID: 26720470) - PS4. The variant is located in a mutational hot spot and/or critical and well-established functional domain (AAA_21; ABC_tran) - PM1. The variant is present at low allele frequencies population databases (rs61750065– gnomAD 0.0001314%; ABraOM no frequency - http://abraom.ib.usp.br/) -PM2_supporting. The p.(Ser1071Leu) was detected in trans with a Pathogenic variant (PMID: 26720470) - PM3. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is Pathogenic
Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel RCV003324508 SCV004030376 pathogenic Cone-rod dystrophy 2023-07-24 criteria provided, single submitter research Clinical significance based on ACMG v2.0
Retina International RCV000085559 SCV000117696 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.