Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001063125 | SCV001227959 | uncertain significance | Neurofibromatosis, type 1 | 2020-05-06 | criteria provided, single submitter | clinical testing | 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). This sequence change replaces tyrosine with cysteine at codon 863 of the NF1 protein (p.Tyr863Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine. 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: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |
Ambry Genetics | RCV002451269 | SCV002739191 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-04-06 | criteria provided, single submitter | clinical testing | The p.Y863C variant (also known as c.2588A>G), located in coding exon 21 of the NF1 gene, results from an A to G substitution at nucleotide position 2588. The tyrosine at codon 863 is replaced by cysteine, 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. |
Gene |
RCV003148922 | SCV003837536 | uncertain significance | not provided | 2022-09-02 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25486365, 2121369) |