Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000684884 | SCV000812345 | uncertain significance | Fanconi anemia | 2021-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine with tyrosine at codon 187 of the FANCC protein (p.Cys187Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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 | RCV002343428 | SCV002648375 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-28 | criteria provided, single submitter | clinical testing | The p.C187Y variant (also known as c.560G>A), located in coding exon 6 of the FANCC gene, results from a G to A substitution at nucleotide position 560. The cysteine at codon 187 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Natera, |
RCV000684884 | SCV002081246 | uncertain significance | Fanconi anemia | 2021-07-15 | no assertion criteria provided | clinical testing |