Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001011488 | SCV001171814 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-01-10 | criteria provided, single submitter | clinical testing | The p.D476G variant (also known as c.1427A>G), located in coding exon 13 of the FANCC gene, results from an A to G substitution at nucleotide position 1427. The aspartic acid at codon 476 is replaced by glycine, an amino acid with similar properties. This amino acid position is not conserved however, glycine is a reference amino acid in several species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV001827177 | SCV002109442 | uncertain significance | Fanconi anemia | 2023-04-23 | criteria provided, single submitter | clinical testing | 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. 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 FANCC protein function. ClinVar contains an entry for this variant (Variation ID: 819172). This variant has not been reported in the literature in individuals affected with FANCC-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 476 of the FANCC protein (p.Asp476Gly). |
Natera, |
RCV001827177 | SCV002081146 | uncertain significance | Fanconi anemia | 2021-09-15 | no assertion criteria provided | clinical testing |