Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001890979 | SCV002164516 | uncertain significance | Neurofibromatosis, type 1 | 2021-11-01 | 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. 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. This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1620 of the NF1 protein (p.Ile1620Val). 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. |
| Ambry Genetics | RCV004558706 | SCV005048256 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-06-21 | criteria provided, single submitter | clinical testing | The p.I1620V variant (also known as c.4858A>G), located in coding exon 36 of the NF1 gene, results from an A to G substitution at nucleotide position 4858. The isoleucine at codon 1620 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |