Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Human Genetics, |
RCV000659985 | SCV000781903 | uncertain significance | Neurofibromatosis, type 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000659985 | SCV001232809 | likely pathogenic | Neurofibromatosis, type 1 | 2019-03-28 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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"). This variant has been observed to be de novo in an individual affected with features consistent with neurofibromatosis, type 1 (Invitae). ClinVar contains an entry for this variant (Variation ID: 547588). This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with serine at codon 443 of the NF1 protein (p.Phe443Ser). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and serine. |