Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001245761 | SCV001419070 | uncertain significance | Neurofibromatosis, type 1 | 2019-10-12 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The aspartic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with NF1-related conditions. This sequence change replaces glutamic acid with aspartic acid at codon 1701 of the NF1 protein (p.Glu1701Asp). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. |
| Ambry Genetics | RCV002348836 | SCV002645817 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-05-12 | criteria provided, single submitter | clinical testing | The p.E1701D variant (also known as c.5103A>T), located in coding exon 36 of the NF1 gene, results from an A to T substitution at nucleotide position 5103. The glutamic acid at codon 1701 is replaced by aspartic acid, 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. |