Submissions for variant NM_020366.4(RPGRIP1):c.2236G>A (p.Gly746Arg)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003788383	SCV004570003	pathogenic	Cone-rod dystrophy 13; Leber congenital amaurosis 6	2023-11-15	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 746 of the RPGRIP1 protein (p.Gly746Arg). This variant is present in population databases (rs535695411, gnomAD 0.003%). This missense change has been observed in individuals with autosomal recessive Leber congenital amaurosis (PMID: 23661368, 24997176, 26355662). 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 RPGRIP1 protein function with a positive predictive value of 80%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV004759292	SCV005374394	likely pathogenic	Leber congenital amaurosis 6	2024-09-22	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV003788383	SCV005637166	likely pathogenic	Cone-rod dystrophy 13; Leber congenital amaurosis 6	2024-02-26	criteria provided, single submitter	clinical testing