Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000523634 | SCV000618354 | uncertain significance | not provided | 2023-04-11 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 22810696, Gordon2000[Book]) |
Invitae | RCV001050994 | SCV001215127 | uncertain significance | Fanconi anemia | 2021-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with glutamine at codon 555 of the FANCC protein (p.Arg555Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs369636116, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with FANCC-related conditions. ClinVar contains an entry for this variant (Variation ID: 449894). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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 | RCV003352901 | SCV004068906 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-06 | criteria provided, single submitter | clinical testing | The p.R555Q variant (also known as c.1664G>A), located in coding exon 14 of the FANCC gene, results from a G to A substitution at nucleotide position 1664. The arginine at codon 555 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate 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. |
Natera, |
RCV001050994 | SCV002081115 | uncertain significance | Fanconi anemia | 2017-10-17 | no assertion criteria provided | clinical testing |