Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001235052 | SCV001407716 | uncertain significance | Neurofibromatosis, type 1 | 2019-10-04 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with serine at codon 721 of the NF1 protein (p.Cys721Ser). The cysteine residue is moderately conserved and there is a moderate physicochemical difference between cysteine and serine. 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. |
| Ambry Genetics | RCV002418808 | SCV002724691 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2021-02-05 | criteria provided, single submitter | clinical testing | The p.C721S variant (also known as c.2161T>A), located in coding exon 18 of the NF1 gene, results from a T to A substitution at nucleotide position 2161. The cysteine at codon 721 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is 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. |