Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002319159 | SCV001172416 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2018-02-15 | criteria provided, single submitter | clinical testing | The p.C509Y variant (also known as c.1526G>A), located in coding exon 13 of the NF1 gene, results from a G to A substitution at nucleotide position 1526. The cysteine at codon 509 is replaced by tyrosine, an amino acid with highly 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. |
| Invitae | RCV001069104 | SCV001234251 | uncertain significance | Neurofibromatosis, type 1 | 2022-10-12 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 819456). This variant has not been reported in the literature in individuals affected with NF1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 509 of the NF1 protein (p.Cys509Tyr). |
| Genome- |
RCV001069104 | SCV002561922 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing |