Submissions for variant NM_000350.3(ABCA4):c.868C>T (p.Arg290Trp)

gnomAD frequency: 0.00001  dbSNP: rs781716640

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Blueprint Genetics	RCV001074574	SCV001240165	pathogenic	Retinal dystrophy	2018-12-31	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001268174	SCV001446896	likely pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001268174	SCV001590588	pathogenic	not provided	2024-11-30	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 290 of the ABCA4 protein (p.Arg290Trp). This variant is present in population databases (rs781716640, gnomAD 0.01%). This missense change has been observed in individual(s) with Stargardt disease (PMID: 17893657, 23419329, 29854428, 29925512). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 866516). 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 disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Laboratory of Medical Genetics, National & Kapodistrian University of Athens	RCV001729794	SCV001976707	pathogenic	Severe early-childhood-onset retinal dystrophy	2021-10-01	criteria provided, single submitter	clinical testing	PM1, PM3, PM5, PP2, PP3, PP5
Revvity Omics, Revvity	RCV001268174	SCV003824319	uncertain significance	not provided	2020-03-27	criteria provided, single submitter	clinical testing
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV001074574	SCV005070582	uncertain significance	Retinal dystrophy	2016-01-01	criteria provided, single submitter	clinical testing
Ophthalmo-Genetics Lab, Instituto de Oftalmologia Conde de Valenciana	RCV004559903	SCV005046931	pathogenic	Stargardt disease 3		no assertion criteria provided	research