Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001057523 | SCV001222021 | uncertain significance | Neurofibromatosis, type 1 | 2021-03-21 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine with leucine at codon 1392 of the NF1 protein (p.Phe1392Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. 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: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with NF1-related conditions. This variant is not present in population databases (ExAC no frequency). |
Ambry Genetics | RCV002327324 | SCV002632745 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-02-02 | criteria provided, single submitter | clinical testing | The p.F1392L variant (also known as c.4174T>C), located in coding exon 31 of the NF1 gene, results from a T to C substitution at nucleotide position 4174. The phenylalanine at codon 1392 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |