Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000539978 | SCV000628645 | uncertain significance | Neurofibromatosis, type 1 | 2023-07-28 | 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: 457743). 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 alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1707 of the NF1 protein (p.Ala1707Val). |
| Ambry Genetics | RCV002341275 | SCV002642233 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2024-06-28 | criteria provided, single submitter | clinical testing | The p.A1707V variant (also known as c.5120C>T), located in coding exon 36 of the NF1 gene, results from a C to T substitution at nucleotide position 5120. The alanine at codon 1707 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 tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |