Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001927233 | SCV002166867 | uncertain significance | Neurofibromatosis, type 1 | 2021-09-10 | 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 expected to disrupt NF1 protein function. This variant has not been reported in the literature in individuals affected with NF1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with valine at codon 257 of the NF1 protein (p.Ala257Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. |
| Ambry Genetics | RCV002397856 | SCV002674442 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2021-02-08 | criteria provided, single submitter | clinical testing | The p.A257V variant (also known as c.770C>T), located in coding exon 8 of the NF1 gene, results from a C to T substitution at nucleotide position 770. The alanine at codon 257 is replaced by valine, 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. |
| Gene |
RCV005232705 | SCV005874481 | uncertain significance | not provided | 2024-09-03 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |