Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001873850 | SCV002117179 | uncertain significance | Neurofibromatosis, type 1 | 2021-08-30 | criteria provided, single submitter | clinical testing | 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. This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with lysine at codon 1041 of the NF1 protein (p.Met1041Lys). The methionine residue is moderately conserved and there is a moderate physicochemical difference between methionine and lysine. |
| Ambry Genetics | RCV002324238 | SCV002607359 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-02-22 | criteria provided, single submitter | clinical testing | The p.M1041K variant (also known as c.3122T>A), located in coding exon 24 of the NF1 gene, results from a T to A substitution at nucleotide position 3122. The methionine at codon 1041 is replaced by lysine, 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. |