Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002316597 | SCV000666643 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-06-27 | criteria provided, single submitter | clinical testing | The p.A761V variant (also known as c.2282C>T), located in coding exon 19 of the NF1 gene, results from a C to T substitution at nucleotide position 2282. The alanine at codon 761 is replaced by valine, 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. |
| Labcorp Genetics |
RCV001221678 | SCV001393738 | uncertain significance | Neurofibromatosis, type 1 | 2024-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 761 of the NF1 protein (p.Ala761Val). This variant is present in population databases (rs746850653, gnomAD 0.007%). 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: 481883). 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) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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. |
| Gene |
RCV001755933 | SCV002006606 | uncertain significance | not provided | 2019-03-25 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
| Genome- |
RCV001221678 | SCV002562023 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing |