Submissions for variant NM_000350.3(ABCA4):c.6104T>C (p.Leu2035Pro)

dbSNP: rs61750642

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000085788	SCV003523317	likely pathogenic	not provided	2023-10-26	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 2035 of the ABCA4 protein (p.Leu2035Pro). 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 and/or Stargardt disease (PMID: 11527935, 14517951, 36909829). ClinVar contains an entry for this variant (Variation ID: 99429). 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%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel	RCV003324514	SCV004030356	likely pathogenic	Stargardt disease	2023-07-24	criteria provided, single submitter	research	Clinical significance based on ACMG v2.0
Retina International	RCV000085788	SCV000117930	not provided	not provided		no assertion provided	not provided