Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000795270 | SCV000934719 | uncertain significance | Fanconi anemia | 2018-10-29 | criteria provided, single submitter | clinical testing | 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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with FANCC-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with leucine at codon 463 of the FANCC protein (p.Ser463Leu). The serine residue is moderately conserved and there is a large physicochemical difference between serine and leucine. 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 | RCV001011218 | SCV001171515 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-22 | criteria provided, single submitter | clinical testing | The p.S463L variant (also known as c.1388C>T), located in coding exon 13 of the FANCC gene, results from a C to T substitution at nucleotide position 1388. The serine at codon 463 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is highly 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. |