Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001246013 | SCV001419340 | uncertain significance | Fanconi anemia | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with arginine at codon 437 of the FANCC protein (p.Gln437Arg). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and arginine. 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. 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 arginine 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. |
Gene |
RCV001586088 | SCV001820173 | uncertain significance | not provided | 2023-02-09 | 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 |
Ambry Genetics | RCV002379941 | SCV002693609 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-08 | criteria provided, single submitter | clinical testing | The p.Q437R variant (also known as c.1310A>G), located in coding exon 12 of the FANCC gene, results from an A to G substitution at nucleotide position 1310. The glutamine at codon 437 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is not 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. |
Fulgent Genetics, |
RCV002484373 | SCV002789023 | uncertain significance | Fanconi anemia complementation group C | 2022-04-22 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001246013 | SCV002081161 | uncertain significance | Fanconi anemia | 2019-10-25 | no assertion criteria provided | clinical testing |