Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002625997 | SCV002964265 | uncertain significance | Neutropenia, severe congenital, 2, autosomal dominant | 2024-04-05 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 128 of the GFI1 protein (p.Ala128Gly). This variant is present in population databases (rs371451553, gnomAD 0.001%). This variant has not been reported in the literature in individuals affected with GFI1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1925455). 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 GFI1 protein function with a negative 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 | RCV004927832 | SCV005593382 | uncertain significance | not specified | 2024-10-05 | criteria provided, single submitter | clinical testing | The p.A128G variant (also known as c.383C>G), located in coding exon 3 of the GFI1 gene, results from a C to G substitution at nucleotide position 383. The alanine at codon 128 is replaced by glycine, 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. |