Submissions for variant NM_000350.3(ABCA4):c.4739T>C (p.Leu1580Ser)

gnomAD frequency: 0.00002  dbSNP: rs777415466

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV000408448	SCV000281903	likely pathogenic	Severe early-childhood-onset retinal dystrophy	2016-01-01	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000761665	SCV000891838	likely pathogenic	not provided	2018-04-01	criteria provided, single submitter	clinical testing
Invitae	RCV000761665	SCV001375259	pathogenic	not provided	2023-10-13	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1580 of the ABCA4 protein (p.Leu1580Ser). This variant is present in population databases (rs777415466, gnomAD 0.02%). This missense change has been observed in individual(s) with inherited retinal dystrophy (PMID: 28118664, 29925512; Invitae). 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: 236121). 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.
Institute of Medical Molecular Genetics, University of Zurich	RCV000408448	SCV001548074	likely pathogenic	Severe early-childhood-onset retinal dystrophy	2021-01-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000761665	SCV001793084	uncertain significance	not provided	2022-12-20	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 22229821, 28118664, 31047443, 30771335, 23882696, 29925512, 19265867, 34426522, 32531858, 35156991, 33546218)
Revvity Omics, Revvity	RCV000761665	SCV003832785	likely pathogenic	not provided	2023-01-12	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000408448	SCV004805110	likely pathogenic	Severe early-childhood-onset retinal dystrophy	2024-03-17	criteria provided, single submitter	research