Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000460273 | SCV000542022 | uncertain significance | Neurofibromatosis, type 1 | 2019-11-07 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with glutamic acid at codon 206 of the NF1 protein (p.Lys206Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a NF1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV004559061 | SCV005048442 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-08-30 | criteria provided, single submitter | clinical testing | The p.K206E variant (also known as c.616A>G), located in coding exon 6 of the NF1 gene, results from an A to G substitution at nucleotide position 616. The lysine at codon 206 is replaced by glutamic acid, an amino acid with similar 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. |