Submissions for variant NM_000350.3(ABCA4):c.3292C>T (p.Arg1098Cys)

gnomAD frequency: 0.00006  dbSNP: rs756840095

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV001074682	SCV000281864	pathogenic	Retinal dystrophy	2020-01-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000478178	SCV000564528	pathogenic	not provided	2023-03-24	criteria provided, single submitter	clinical testing	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: 10958763, 11702214, 17982420, 28559085, 29925512, 19265867, 30060493, 29178665, 19074458, 34426522, 31589614, 35119454, 32531858, 32619608, Saleh2021[noPMID])
Blueprint Genetics	RCV001074682	SCV001240275	pathogenic	Retinal dystrophy	2019-03-21	criteria provided, single submitter	clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001196593	SCV001367201	likely pathogenic	Age related macular degeneration 2	2020-02-04	criteria provided, single submitter	clinical testing	This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM1,PM2,PP3.
CeGaT Center for Human Genetics Tuebingen	RCV000478178	SCV001501909	likely pathogenic	not provided	2023-03-01	criteria provided, single submitter	clinical testing	ABCA4: PM1, PM2, PP1, PP3
Labcorp Genetics (formerly Invitae), Labcorp	RCV000478178	SCV001585366	pathogenic	not provided	2024-12-30	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1098 of the ABCA4 protein (p.Arg1098Cys). This variant is present in population databases (rs756840095, gnomAD 0.006%). This missense change has been observed in individual(s) with Stargardt disease or cone rod distrophy (PMID: 19074458, 23096905, 28559085, 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: 236100). 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.
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV004796121	SCV005418273	pathogenic	Cone-rod dystrophy 3; Age related macular degeneration 2; Severe early-childhood-onset retinal dystrophy; Retinitis pigmentosa 19		criteria provided, single submitter	clinical testing	PM2_Supporting+PP3_Moderate+PM3_VeryStrong
Ophthalmo-Genetics Lab, Instituto de Oftalmologia Conde de Valenciana	RCV000408518	SCV005046999	pathogenic	Severe early-childhood-onset retinal dystrophy		no assertion criteria provided	research