Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001896831 | SCV002172578 | uncertain significance | Neurofibromatosis, type 1 | 2023-06-14 | 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 expected to disrupt NF1 protein function. ClinVar contains an entry for this variant (Variation ID: 1400995). 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 lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 490 of the NF1 protein (p.Lys490Glu). |
| Ambry Genetics | RCV002388799 | SCV002697488 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2024-12-06 | criteria provided, single submitter | clinical testing | The p.K490E variant (also known as c.1468A>G), located in coding exon 13 of the NF1 gene, results from an A to G substitution at nucleotide position 1468. The lysine at codon 490 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. 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. |