Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002400184 | SCV001180279 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2019-12-19 | criteria provided, single submitter | clinical testing | The p.D1059V variant (also known as c.3176A>T), located in coding exon 24 of the NF1 gene, results from an A to T substitution at nucleotide position 3176. The aspartic acid at codon 1059 is replaced by valine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV001873315 | SCV002203333 | uncertain significance | Neurofibromatosis, type 1 | 2023-09-05 | criteria provided, single submitter | clinical testing | 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 not expected to disrupt NF1 protein function. This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 1059 of the NF1 protein (p.Asp1059Val). 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: 823080). 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. |
Genome- |
RCV001873315 | SCV002560270 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing |