Submissions for variant NM_000350.3(ABCA4):c.1933G>A (p.Asp645Asn)

dbSNP: rs61749418

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000085447	SCV001215910	pathogenic	not provided	2023-10-15	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 645 of the ABCA4 protein (p.Asp645Asn). This variant is present in population databases (rs61749418, gnomAD 0.004%). This missense change has been observed in individual(s) with Stargardt disease and retinitis pigmentosa (PMID: 9973280, 28559085, 29975949, 30029497, 31144483). 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: 99103). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ABCA4 protein function. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics	RCV001074983	SCV001240592	pathogenic	Retinal dystrophy	2017-11-12	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000085447	SCV001245786	pathogenic	not provided	2017-06-01	criteria provided, single submitter	clinical testing
Retina International	RCV000085447	SCV000117584	not provided	not provided		no assertion provided	not provided