Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001992657 | SCV002225785 | uncertain significance | Neurofibromatosis, type 1 | 2021-08-12 | 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 not expected to disrupt NF1 protein function. This variant has not been reported in the literature in individuals affected with NF1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with aspartic acid at codon 1619 of the NF1 protein (p.Glu1619Asp). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. |
| Ambry Genetics | RCV004996145 | SCV005451936 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2024-06-29 | criteria provided, single submitter | clinical testing | The p.E1619D variant (also known as c.4857A>C), located in coding exon 36 of the NF1 gene, results from an A to C substitution at nucleotide position 4857. The glutamic acid at codon 1619 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |