Submissions for variant NM_000350.3(ABCA4):c.5527C>T (p.Arg1843Trp)

dbSNP: rs62642576

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000085736	SCV000780283	likely pathogenic	not provided	2017-11-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000085736	SCV001532727	pathogenic	not provided	2024-10-22	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1843 of the ABCA4 protein (p.Arg1843Trp). This variant is present in population databases (rs62642576, gnomAD 0.007%). This missense change has been observed in individuals with Stargardt disease (PMID: 9973280, 24409374, 26780318, 32307445; internal data). ClinVar contains an entry for this variant (Variation ID: 99382). 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.
GeneDx	RCV000085736	SCV004034954	likely pathogenic	not provided	2023-03-10	criteria provided, single submitter	clinical testing	Observed with two additional variants in the ABCA4 gene in patients with Stargardt disease in published literature, although it is not known what combination of these variants occurred on the same (in cis) or on different (in trans) chromosomes (Verdina et al., 2012; Jiang et al., 2016); Not observed at significant frequency in large population cohorts (gnomAD); Published functional studies suggest this variant results in moderate/mild impairment of the structure and function of the protein, but additional studies are needed to determine the functional effect of this variant in vivo (Garces et al., 2020); 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: 26780318, 33375396, 9973280, 32307445, 32531858, 24409374)
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004815124	SCV005069869	likely pathogenic	Retinal dystrophy	2021-01-01	criteria provided, single submitter	clinical testing
Retina International	RCV000085736	SCV000117877	not provided	not provided		no assertion provided	not provided
Ophthalmo-Genetics Lab, Instituto de Oftalmologia Conde de Valenciana	RCV004562248	SCV005049254	pathogenic	Severe early-childhood-onset retinal dystrophy		no assertion criteria provided	research