Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000812451 | SCV000952764 | uncertain significance | Neurofibromatosis, type 1 | 2018-10-10 | 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. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with NF1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tryptophan with serine at codon 425 of the NF1 protein (p.Trp425Ser). The tryptophan residue is highly conserved and there is a large physicochemical difference between tryptophan and serine. |
| Ambry Genetics | RCV002370190 | SCV002686795 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2021-07-14 | criteria provided, single submitter | clinical testing | The p.W425S variant (also known as c.1274G>C), located in coding exon 12 of the NF1 gene, results from a G to C substitution at nucleotide position 1274. The tryptophan at codon 425 is replaced by serine, an amino acid with highly dissimilar 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. |