Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001961266 | SCV002253410 | uncertain significance | not provided | 2023-04-24 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid with aspartic acid at codon 155 of the GUCA1A protein (p.Glu155Asp). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant has not been reported in the literature in individuals affected with GUCA1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 1464056). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects GUCA1A function (PMID: 9425045). This variant disrupts the p.Glu155 amino acid residue in GUCA1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11484154, 28559085). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Mendelics | RCV002246629 | SCV002517272 | likely pathogenic | Cone dystrophy 3 | 2022-05-04 | criteria provided, single submitter | clinical testing |