Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001067475 | SCV001232541 | uncertain significance | Neurofibromatosis, type 1 | 2019-02-02 | 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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been observed in an individual with neurofibromatosis type 1 (Invitae). However, in that individual a pathogenic allele was also identified in NF1, which suggests that this c.1207C>A variant was not the primary cause of disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with threonine at codon 403 of the NF1 protein (p.Pro403Thr). The proline residue is highly conserved and there is a small physicochemical difference between proline and threonine. |