Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002051515 | SCV002112896 | uncertain significance | Neurofibromatosis, type 1 | 2021-05-04 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 924 of the NF1 protein (p.Glu924Asp). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. |
| Ambry Genetics | RCV004558669 | SCV005047613 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-12-06 | criteria provided, single submitter | clinical testing | The p.E924D variant (also known as c.2772A>C), located in coding exon 21 of the NF1 gene, results from an A to C substitution at nucleotide position 2772. The glutamic acid at codon 924 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |