Submissions for variant NM_000350.3(ABCA4):c.4919G>A (p.Arg1640Gln)

gnomAD frequency: 0.00001  dbSNP: rs61751403

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV000321118	SCV000281908	pathogenic	Severe early-childhood-onset retinal dystrophy	2016-01-01	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000085684	SCV000336550	pathogenic	not provided	2015-10-27	criteria provided, single submitter	clinical testing
GeneDx	RCV000085684	SCV000511902	pathogenic	not provided	2021-12-22	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published functional studies demonstrate that the c.4919 G>A variant may have a negative effect on proper splicing (Schulz et al., 2017); This variant is associated with the following publications: (PMID: 26743751, 11527935, 11379881, 10711710, 23755871, 26377081, 26103963, 25082885, 19074458, 28118664, 28041643, 29925512, 31736247, 31456290, 30718709, 32581362, 31589614, 32037395)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000085684	SCV001198188	pathogenic	not provided	2024-12-04	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1640 of the ABCA4 protein (p.Arg1640Gln). This variant is present in population databases (rs61751403, gnomAD 0.009%). This missense change has been observed in individuals with autosomal recessive ABCA4-related conditions (PMID: 10711710, 11527935, 23755871, 26103963). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 99331). 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%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics	RCV000504816	SCV001239057	pathogenic	Retinal dystrophy	2019-04-25	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000085684	SCV001334599	pathogenic	not provided	2020-02-01	criteria provided, single submitter	clinical testing
Institute of Medical Molecular Genetics, University of Zurich	RCV000321118	SCV001548083	likely pathogenic	Severe early-childhood-onset retinal dystrophy	2021-01-30	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV003223338	SCV003918846	pathogenic	Cone-rod dystrophy 3	2023-04-21	criteria provided, single submitter	clinical testing
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV000504816	SCV005072391	pathogenic	Retinal dystrophy	2023-01-01	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000321118	SCV005368317	pathogenic	Severe early-childhood-onset retinal dystrophy	2024-08-20	criteria provided, single submitter	clinical testing	Criteria applied: PM3_VSTR,PM5,PM2_SUP,PP3; Identified as compund heterozygous with NM_000350.3:c.2012_2013del
Fulgent Genetics, Fulgent Genetics	RCV005031587	SCV005658801	pathogenic	Cone-rod dystrophy 3; Age related macular degeneration 2; Severe early-childhood-onset retinal dystrophy; Retinitis pigmentosa 19	2024-02-16	criteria provided, single submitter	clinical testing
Retina International	RCV000085684	SCV000117824	not provided	not provided		no assertion provided	not provided
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000504816	SCV000598987	uncertain significance	Retinal dystrophy	2015-01-01	no assertion criteria provided	research
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV000787505	SCV000926471	pathogenic	Stargardt disease	2018-04-01	no assertion criteria provided	research
Sharon lab, Hadassah-Hebrew University Medical Center	RCV000787505	SCV001160838	pathogenic	Stargardt disease	2019-06-23	no assertion criteria provided	research
Ophthalmo-Genetics Lab, Instituto de Oftalmologia Conde de Valenciana	RCV000321118	SCV005047040	pathogenic	Severe early-childhood-onset retinal dystrophy		no assertion criteria provided	research