Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000567655 | SCV000673345 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-25 | criteria provided, single submitter | clinical testing | The p.P541L variant (also known as c.1622C>T), located in coding exon 14 of the FANCC gene, results from a C to T substitution at nucleotide position 1622. The proline at codon 541 is replaced by leucine, an amino acid with 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. |
Invitae | RCV000630828 | SCV000751796 | uncertain significance | Fanconi anemia | 2021-08-24 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with leucine at codon 541 of the FANCC protein (p.Pro541Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine. 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 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. |
Gene |
RCV002293461 | SCV002586867 | uncertain significance | not provided | 2022-04-20 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Natera, |
RCV000630828 | SCV002081123 | uncertain significance | Fanconi anemia | 2020-02-21 | no assertion criteria provided | clinical testing |