Submissions for variant NM_000350.3(ABCA4):c.1715G>A (p.Arg572Gln)

gnomAD frequency: 0.00005  dbSNP: rs61748559

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV000008357	SCV000281827	likely pathogenic	Severe early-childhood-onset retinal dystrophy	2016-01-01	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000085416	SCV000343783	uncertain significance	not provided	2016-08-08	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000085416	SCV000780286	uncertain significance	not provided	2018-03-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000085416	SCV001198189	likely pathogenic	not provided	2024-11-12	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 572 of the ABCA4 protein (p.Arg572Gln). This variant is present in population databases (rs61748559, gnomAD 0.007%). This missense change has been observed in individual(s) with retinal disease, always in combination (often proven in cis) with the Pathogenic (low penetrance) variant p.Gly863Ala (PMID: 9973280, 10958763, 20647261, 28118664, 29555955, 29925512). ClinVar contains an entry for this variant (Variation ID: 7900). 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%. This variant disrupts the p.Arg572 amino acid residue in ABCA4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8533764, 9973280). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Blueprint Genetics	RCV001074326	SCV001239900	uncertain significance	Retinal dystrophy	2019-07-09	criteria provided, single submitter	clinical testing
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV001074326	SCV005072204	likely pathogenic	Retinal dystrophy	2018-01-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV005031425	SCV005663536	likely pathogenic	Cone-rod dystrophy 3; Age related macular degeneration 2; Severe early-childhood-onset retinal dystrophy; Retinitis pigmentosa 19	2024-04-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000085416	SCV005689703	uncertain significance	not provided	2024-08-08	criteria provided, single submitter	clinical testing	Observed with pathogenic variant(s) and likely benign/benign variant(s) on the same allele (in cis), on opposite allele (in trans), and phase unknown in multiple unrelated individuals in published literature (PMID: 9973280, 29555955, 29884405, 28118664, 20647261, 10746567, 29925512); 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: 36464167, 9973280, 29555955, 29884405, 10958763, 27939946, 16123440, 11702214, 28118664, 20647261, 10746567, 11923272, 38219857, 33090715, 32037395, 29925512, 35120629, 31964843)
OMIM	RCV000008357	SCV000028565	pathogenic	Severe early-childhood-onset retinal dystrophy	2000-02-01	no assertion criteria provided	literature only
Retina International	RCV000085416	SCV000117553	not provided	not provided		no assertion provided	not provided