Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001987457 | SCV002221494 | uncertain significance | Neurofibromatosis, type 1 | 2021-07-28 | criteria provided, single submitter | clinical testing | 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. This variant has not been reported in the literature in individuals affected with NF1-related conditions. This sequence change replaces lysine with arginine at codon 1036 of the NF1 protein (p.Lys1036Arg). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and arginine. This variant is not present in population databases (ExAC no frequency). |
| Ambry Genetics | RCV002324388 | SCV002605939 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-01-12 | criteria provided, single submitter | clinical testing | The p.K1036R variant (also known as c.3107A>G), located in coding exon 23 of the NF1 gene, results from an A to G substitution at nucleotide position 3107. The lysine at codon 1036 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |