Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001304877 | SCV001494182 | uncertain significance | Sulfite oxidase deficiency due to molybdenum cofactor deficiency type C | 2024-07-06 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 443 of the GPHN protein (p.Arg443Gln). This variant is present in population databases (rs745338809, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with GPHN-related conditions. ClinVar contains an entry for this variant (Variation ID: 1007658). 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 GPHN protein function with a positive predictive value of 80%. 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. |
| Ambry Genetics | RCV002544986 | SCV003582365 | uncertain significance | Inborn genetic diseases | 2021-10-21 | criteria provided, single submitter | clinical testing | The c.1328G>A (p.R443Q) alteration is located in exon 14 (coding exon 14) of the GPHN gene. This alteration results from a G to A substitution at nucleotide position 1328, causing the arginine (R) at amino acid position 443 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |