Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001297155 | SCV001486141 | uncertain significance | Neurofibromatosis, type 2 | 2020-01-08 | 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with NF2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with glutamic acid at codon 523 of the NF2 protein (p.Lys523Glu). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamic acid. |
Ambry Genetics | RCV002402825 | SCV002708764 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-14 | criteria provided, single submitter | clinical testing | The p.K523E variant (also known as c.1567A>G), located in coding exon 14 of the NF2 gene, results from an A to G substitution at nucleotide position 1567. The lysine at codon 523 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. 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. |