Submissions for variant NM_000350.3(ABCA4):c.5929G>A (p.Gly1977Ser)

gnomAD frequency: 0.00001  dbSNP: rs61750639

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000085778	SCV000322151	pathogenic	not provided	2019-08-30	criteria provided, single submitter	clinical testing	Published functional studies demonstrate a damaging effect with significantly reduced ATPase activity compared to wild type (Sun et al., 2000); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 28365912, 23755871, 19028736, 11017087, 11527935, 17325136, 10958763, 27739528, 29555955, 9781034, 16917483, 29925512, 32141364, 31456290, 32845050)
Invitae	RCV000085778	SCV001230080	pathogenic	not provided	2023-12-11	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1977 of the ABCA4 protein (p.Gly1977Ser). This variant is present in population databases (rs61750639, gnomAD 0.003%). This missense change has been observed in individual(s) with Stargardt disease (PMID: 9781034, 23755871, 27739528, 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: 99421). 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 with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics	RCV001075771	SCV001241403	pathogenic	Retinal dystrophy	2019-06-26	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000085778	SCV001448013	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Dept Of Ophthalmology, Nagoya University	RCV001075771	SCV004706470	pathogenic	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research
Retina International	RCV000085778	SCV000117920	not provided	not provided		no assertion provided	not provided
Sharon lab, Hadassah-Hebrew University Medical Center	RCV001002809	SCV001160821	likely pathogenic	Retinitis pigmentosa	2019-06-23	no assertion criteria provided	research