Submissions for variant NM_000350.3(ABCA4):c.286A>G (p.Asn96Asp)

dbSNP: rs61748529

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Mendelics	RCV000986376	SCV001135366	pathogenic	Severe early-childhood-onset retinal dystrophy	2019-05-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000085515	SCV001222272	pathogenic	not provided	2025-01-06	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 96 of the ABCA4 protein (p.Asn96Asp). This variant is present in population databases (rs61748529, gnomAD 0.003%). This missense change has been observed in individuals with Stargardt disease (PMID: 19365591, 28355279, 29925512, 30060493, 30093795). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 99166). 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.
CeGaT Center for Human Genetics Tuebingen	RCV000085515	SCV001247763	pathogenic	not provided	2018-02-01	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000986376	SCV001950068	likely pathogenic	Severe early-childhood-onset retinal dystrophy	2021-07-02	criteria provided, single submitter	clinical testing	This variant was identified as compound heterozygous with NM_000350.3:c.666_678del.
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV000986376	SCV002767212	pathogenic	Severe early-childhood-onset retinal dystrophy	2021-05-06	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with retinal dystrophy, Stargardt disease 1 (MIM#248200) and cone-rod dystrophy (MIM#604116). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0115 - Variants in this gene are known to have variable expressivity. Affected siblings can have variable age of onset and severity of disease (PMID:31522899). 0200 - Variant is predicted to result in a missense amino acid change from asparagine to aspartic acid. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v3) (3 heterozygotes, 0 homozygotes). (SP) 0309 - An alternative amino acid change p.(Asn96His) at the same position has been observed in gnomAD (v3) (1 heterozygote, 0 homozygotes). (I) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has previously been reported in both the homozygous and compound heterozygous state in at least 10 individuals with Stargardt disease (ClinVar; PMID: 19365591; 25444351; 30093795; 29625472; 30060493). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004815092	SCV005071327	likely pathogenic	Retinal dystrophy	2020-01-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV005025150	SCV005656541	pathogenic	Cone-rod dystrophy 3; Age related macular degeneration 2; Severe early-childhood-onset retinal dystrophy; Retinitis pigmentosa 19	2024-05-16	criteria provided, single submitter	clinical testing
Retina International	RCV000085515	SCV000117652	not provided	not provided		no assertion provided	not provided
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000085515	SCV001808415	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000085515	SCV001958650	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000085515	SCV002034591	likely pathogenic	not provided		no assertion criteria provided	clinical testing