Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001926962 | SCV002198864 | uncertain significance | Neurofibromatosis, type 1 | 2021-01-19 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with arginine at codon 2261 of the NF1 protein (p.Pro2261Arg). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NF1-related conditions. 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"). 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 | RCV002361254 | SCV002662483 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-04-10 | criteria provided, single submitter | clinical testing | The p.P2261R variant (also known as c.6782C>G), located in coding exon 45 of the NF1 gene, results from a C to G substitution at nucleotide position 6782. The proline at codon 2261 is replaced by arginine, an amino acid with 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. |