Submissions for variant NM_000350.3(ABCA4):c.746A>G (p.Asp249Gly)

dbSNP: rs62646865

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000085864	SCV001222927	pathogenic	not provided	2024-12-02	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 249 of the ABCA4 protein (p.Asp249Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of ABCA4-related conditions (PMID: 9973280, 28559085, 32531858; internal data). 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: 99503). 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.
CeGaT Center for Human Genetics Tuebingen	RCV000085864	SCV001502527	uncertain significance	not provided	2020-07-01	criteria provided, single submitter	clinical testing
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004815138	SCV005072406	likely pathogenic	Retinal dystrophy	2018-01-01	criteria provided, single submitter	clinical testing
Retina International	RCV000085864	SCV000118007	not provided	not provided		no assertion provided	not provided