Submissions for variant NM_000350.3(ABCA4):c.2023G>A (p.Val675Ile)

gnomAD frequency: 0.00001  dbSNP: rs575453437

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000478104	SCV000342424	likely pathogenic	not provided	2016-08-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000478104	SCV000564522	likely pathogenic	not provided	2024-12-17	criteria provided, single submitter	clinical testing	In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31589614, 23499370, 26024099, 30798147, 29925512, 26593885, 28041643, 32581362, 32619608, 36969552, 35119454, 36284460, 32483926, 28181551, 38317096, 35120629, 31964843, 28327576, 35657619)
CeGaT Center for Human Genetics Tuebingen	RCV000478104	SCV000608480	likely pathogenic	not provided	2017-04-01	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV001074658	SCV001240250	likely pathogenic	Retinal dystrophy	2019-02-22	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000478104	SCV001421498	pathogenic	not provided	2024-11-21	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 675 of the ABCA4 protein (p.Val675Ile). This variant is present in population databases (rs575453437, gnomAD 0.04%). This missense change has been observed in individuals with Stargardt disease (PMID: 23499370, 26593885, 28041643, 30060493). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 288341). 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%. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV005025432	SCV005661360	likely pathogenic	Cone-rod dystrophy 3; Age related macular degeneration 2; Severe early-childhood-onset retinal dystrophy; Retinitis pigmentosa 19	2024-06-21	criteria provided, single submitter	clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000329208	SCV000598947	likely pathogenic	Severe early-childhood-onset retinal dystrophy	2015-01-01	no assertion criteria provided	research
Ophthalmo-Genetics Lab, Instituto de Oftalmologia Conde de Valenciana	RCV004558613	SCV005046940	pathogenic	Stargardt disease 3		no assertion criteria provided	research