Submissions for variant NM_000350.3(ABCA4):c.2041C>T (p.Arg681Ter) (rs61749423)

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Human Genetics, Univ. Regensburg,Univ. Regensburg	RCV000408512	SCV000281841	pathogenic	Stargardt disease 1	2016-01-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000085458	SCV000490370	pathogenic	not provided	2018-09-28	criteria provided, single submitter	clinical testing	The R681X nonsense variant in the ABCA4 gene has previously been reported in association with Stargardt disease and cone-rod dystrophy (Maugeri et al., 1999; Jaakson et al., 2003; Cideciyan et al., 2009) and is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. We interpret this variant as pathogenic.
Blueprint Genetics	RCV001073628	SCV001239179	pathogenic	Retinal dystrophy	2019-07-20	criteria provided, single submitter	clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000085458	SCV001245781	pathogenic	not provided	2017-08-01	criteria provided, single submitter	clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana	RCV001195987	SCV001366414	pathogenic	Age-related macular degeneration 2	2019-08-21	criteria provided, single submitter	clinical testing	This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2,PP3,PP5.
Invitae	RCV000085458	SCV001393043	pathogenic	not provided	2019-11-04	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg681*) in the ABCA4 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs61749423, ExAC 0.006%). This variant has been observed in many individuals and a family affected with retinal disease (PMID: 25544989, 28041643, 28559085, 10090887). ClinVar contains an entry for this variant (Variation ID: 99114). Loss-of-function variants in ABCA4 are known to be pathogenic (PMID: 10958761, 24938718, 25312043, 26780318). For these reasons, this variant has been classified as Pathogenic.
Retina International	RCV000085458	SCV000117595	not provided	not provided		no assertion provided	not provided
Centre for Genomic Medicine, Manchester,Central Manchester University Hospitals	RCV000210310	SCV000259074	likely pathogenic	Bull's eye maculopathy	2015-01-19	no assertion criteria provided	clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000504983	SCV000598948	pathogenic	Leber congenital amaurosis	2015-01-01	no assertion criteria provided	research