Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000559851 | SCV000628469 | likely pathogenic | Neurofibromatosis, type 1 | 2020-03-17 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with arginine at codon 965 of the NF1 protein (p.Ile965Arg). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and arginine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a NF1-related disease. Family studies have indicated that this variant was not present in the parents of an individual with clinical features of neurofibromatosis type 1, which suggests that it was de novo in that affected individual (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change that has been observed de novo in an affected individual. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |