Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001342398 | SCV001536326 | uncertain significance | Neurofibromatosis, type 1 | 2024-12-15 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 181 of the NF1 protein (p.Gln181Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1039009). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt NF1 protein function with a positive predictive value of 95%. 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 | RCV004557551 | SCV005048335 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-05-10 | criteria provided, single submitter | clinical testing | The p.Q181R variant (also known as c.542A>G), located in coding exon 5 of the NF1 gene, results from an A to G substitution at nucleotide position 542. The glutamine at codon 181 is replaced by arginine, an amino acid with highly 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. |