Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000812034 | SCV000952332 | uncertain significance | Neurofibromatosis, type 1 | 2018-10-26 | criteria provided, single submitter | clinical testing | 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 isoleucine with asparagine at codon 2191 of the NF1 protein (p.Ile2191Asn). The isoleucine residue is moderately conserved and there is a large physicochemical difference between isoleucine and asparagine. 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: "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 | RCV002363106 | SCV002664822 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-05-02 | criteria provided, single submitter | clinical testing | The p.I2191N variant (also known as c.6572T>A), located in coding exon 42 of the NF1 gene, results from a T to A substitution at nucleotide position 6572. The isoleucine at codon 2191 is replaced by asparagine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |