Submissions for variant NM_000350.3(ABCA4):c.1988G>A (p.Trp663Ter)

dbSNP: rs865990202

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000414150	SCV000490369	pathogenic	not provided	2016-07-19	criteria provided, single submitter	clinical testing	The W663X pathogenic variant has been reported multiple times in individuals with Stargardt disease and retinal dystrophy (Rivera et al., 2000; Burke et al., 2012; Tiwari et al., 2016). The G1203E variant has been reported in association with autosomal recessive code-rod dystrophy, however specific clinical and segregation information was not provided (Kitiratschky et al., 2008; Zlotogora et al., 2010). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay.
CeGaT Center for Human Genetics Tuebingen	RCV000414150	SCV001245783	pathogenic	not provided	2017-04-01	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000414150	SCV001447307	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Institute of Medical Molecular Genetics, University of Zurich	RCV001353030	SCV001548143	likely pathogenic	Retinitis pigmentosa 19	2021-01-30	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000414150	SCV001590409	pathogenic	not provided	2021-01-29	criteria provided, single submitter	clinical testing	Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This sequence change creates a premature translational stop signal (p.Trp663*) in the ABCA4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCA4 are known to be pathogenic (PMID: 10958761, 24938718, 25312043, 26780318). This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Stargradt disease (PMID: 10958763, 28559085). ClinVar contains an entry for this variant (Variation ID: 372289). For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004816637	SCV005069627	pathogenic	Retinal dystrophy	2021-01-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV005027469	SCV005661379	pathogenic	Cone-rod dystrophy 3; Age related macular degeneration 2; Severe early-childhood-onset retinal dystrophy; Retinitis pigmentosa 19	2024-04-16	criteria provided, single submitter	clinical testing