Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000463192 | SCV000542071 | pathogenic | Neurofibromatosis, type 1 | 2022-03-29 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Asn1430 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12787671, 21567923, 27322474, 28422438). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. 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: 68348). This missense change has been observed in individuals with NF1-related conditions (PMID: 16380919; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 1430 of the NF1 protein (p.Asn1430Thr). |
| Center for Human Genetics, |
RCV000463192 | SCV000782021 | pathogenic | Neurofibromatosis, type 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002326782 | SCV002631798 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2020-01-02 | criteria provided, single submitter | clinical testing | The p.N1430T variant (also known as c.4289A>C), located in coding exon 32 of the NF1 gene, results from an A to C substitution at nucleotide position 4289. The asparagine at codon 1430 is replaced by threonine, 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. |
| Uni |
RCV000059201 | SCV000090730 | not provided | not provided | no assertion provided | not provided |