Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001216688 | SCV001388497 | uncertain significance | Autosomal recessive severe congenital neutropenia due to G6PC3 deficiency | 2023-10-05 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 296 of the G6PC3 protein (p.Pro296Leu). This variant is present in population databases (rs779143230, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with G6PC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 945932). 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 not expected to disrupt G6PC3 protein function. 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 | RCV002562416 | SCV003526580 | uncertain significance | Inborn genetic diseases | 2024-12-10 | criteria provided, single submitter | clinical testing | The p.P296L variant (also known as c.887C>T), located in coding exon 6 of the G6PC3 gene, results from a C to T substitution at nucleotide position 887. The proline at codon 296 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |