Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001377421 | SCV001574752 | pathogenic | Cone-rod dystrophy 6; Leber congenital amaurosis 1 | 2023-05-11 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects GUCY2D function (PMID: 25477517). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GUCY2D protein function. ClinVar contains an entry for this variant (Variation ID: 98536). This missense change has been observed in individuals with clinical features of autosomal recessive Leber congenital amaurosis (PMID: 15024725, 17525851, 32865313; Invitae). This variant is present in population databases (rs61749676, gnomAD 0.007%). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 351 of the GUCY2D protein (p.Tyr351Cys). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003398694 | SCV004122666 | likely pathogenic | Leber congenital amaurosis | 2023-10-10 | criteria provided, single submitter | clinical testing | Variant summary: GUCY2D c.1052A>G (p.Tyr351Cys) results in a non-conservative amino acid change located in the Receptor, ligand binding region (IPR001828) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.3e-06 in 240812 control chromosomes (gnomAD). c.1052A>G has been reported in the literature in individuals affected with Leber Congenital Amaurosis (examples: Hanein_2004, Preising_2007, Sallum_2020). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence that this variant reduced the guanylate cyclase 1 (GC1)-retinal degeneration 3 (RD3) complex binding efficiency (Zullinger_2015). The following publications have been ascertained in the context of this evaluation (PMID: 15024725, 32865313, 25477517, 17525851 ). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Retina International | RCV000084827 | SCV000116963 | not provided | not provided | no assertion provided | not provided | ||
| Laboratory of Genetics in Ophthalmology, |
RCV001250829 | SCV001426316 | likely pathogenic | Leber congenital amaurosis 1 | no assertion criteria provided | research |