Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001928036 | SCV002182075 | uncertain significance | Neurofibromatosis, type 1 | 2021-08-09 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with asparagine at codon 1823 of the NF1 protein (p.Lys1823Asn). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with NF1-related conditions. 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 expected to disrupt NF1 protein function. 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 | RCV002344015 | SCV002653866 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-02-12 | criteria provided, single submitter | clinical testing | The p.K1823N variant (also known as c.5469G>T), located in coding exon 37 of the NF1 gene, results from a G to T substitution at nucleotide position 5469. The lysine at codon 1823 is replaced by asparagine, an amino acid with similar 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. |