Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000160494 | SCV000211059 | uncertain significance | not provided | 2023-07-24 | 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 |
Invitae | RCV000630940 | SCV000751915 | uncertain significance | Fanconi anemia | 2021-08-26 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with glutamine at codon 548 of the FANCC protein (p.Arg548Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). 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: 182492). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 | RCV001012509 | SCV001172969 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-22 | criteria provided, single submitter | clinical testing | The p.R548Q variant (also known as c.1643G>A), located in coding exon 14 of the FANCC gene, results from a G to A substitution at nucleotide position 1643. The arginine at codon 548 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is well 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. |
Genetic Services Laboratory, |
RCV001818357 | SCV002069935 | uncertain significance | not specified | 2019-11-26 | criteria provided, single submitter | clinical testing | |
St. |
RCV003153437 | SCV003843181 | uncertain significance | Fanconi anemia complementation group C | 2022-12-06 | criteria provided, single submitter | clinical testing | The FANCC c.1643G>A (p.Arg548Gln) missense change has a maximum subpopulation frequency of 0.0065% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with Fanconi anemia. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |
Natera, |
RCV000630940 | SCV002081119 | uncertain significance | Fanconi anemia | 2018-04-28 | no assertion criteria provided | clinical testing |