Submissions for variant NM_000350.3(ABCA4):c.1819G>A (p.Gly607Arg)

gnomAD frequency: 0.00004  dbSNP: rs61749412

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV000408475	SCV000281832	likely pathogenic	Severe early-childhood-onset retinal dystrophy	2016-01-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000085431	SCV001218585	pathogenic	not provided	2024-01-18	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 607 of the ABCA4 protein (p.Gly607Arg). This variant is present in population databases (rs61749412, gnomAD 0.01%). This missense change has been observed in individual(s) with Stargardt disease (PMID: 23755871, 24632595, 24763286, 28559085). 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: 99087). 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%. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics	RCV001075859	SCV001241498	pathogenic	Retinal dystrophy	2019-08-08	criteria provided, single submitter	clinical testing
Institute of Medical Molecular Genetics, University of Zurich	RCV000408475	SCV001548113	likely pathogenic	Severe early-childhood-onset retinal dystrophy	2021-01-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000085431	SCV002097409	pathogenic	not provided	2024-11-24	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: 33546218, 35120629, 35260635, 31964843, 36460718, 36729443, 10958763, 31429209, 32531858, 34315337, 27032803, 23096905, 24763286, 25066811, 24632595, 28041643, 12515255, 18652558, 23755871, 28118664, 30416334, 29925512, 28559085, 31980526, 32845068, 32581362, 32619608, 33173045, 33301772, 35119454, 38219857)
CeGaT Center for Human Genetics Tuebingen	RCV000085431	SCV004702250	pathogenic	not provided	2024-01-01	criteria provided, single submitter	clinical testing	ABCA4: PM3:Very Strong, PP1:Strong, PS1, PM2, PM5, PP3
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV001075859	SCV005070971	likely pathogenic	Retinal dystrophy	2021-01-01	criteria provided, single submitter	clinical testing
Retina International	RCV000085431	SCV000117568	not provided	not provided		no assertion provided	not provided
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000408475	SCV000598943	likely pathogenic	Severe early-childhood-onset retinal dystrophy	2015-01-01	no assertion criteria provided	research
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV000787762	SCV000926767	likely pathogenic	Stargardt disease	2018-04-01	no assertion criteria provided	research