Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001347414 | SCV001541672 | uncertain significance | Neurofibromatosis, type 1 | 2020-09-10 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NF1 protein function. This variant has not been reported in the literature in individuals with NF1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with asparagine at codon 2477 of the NF1 protein (p.Lys2477Asn). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and asparagine. |
| Ambry Genetics | RCV002384484 | SCV002671657 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-07-29 | criteria provided, single submitter | clinical testing | The p.K2477N variant (also known as c.7431A>C), located in coding exon 50 of the NF1 gene, results from an A to C substitution at nucleotide position 7431. The lysine at codon 2477 is replaced by asparagine, an amino acid with similar properties. This amino acid position is conserved. 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. |