Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001057747 | SCV001222256 | uncertain significance | Neurofibromatosis, type 1 | 2020-03-18 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with NF1-related conditions. 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. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tyrosine at codon 2233 of the NF1 protein (p.Cys2233Tyr). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and tyrosine. |
| Ambry Genetics | RCV003160463 | SCV003854943 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-03-15 | criteria provided, single submitter | clinical testing | The p.C2233Y variant (also known as c.6698G>A), located in coding exon 44 of the NF1 gene, results from a G to A substitution at nucleotide position 6698. The cysteine at codon 2233 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |