Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001051977 | SCV001216162 | pathogenic | Neurofibromatosis, type 1 | 2020-01-07 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NF1 protein function. This variant has been observed in individual(s) with neurofibromatosis type 1 (PMID: 30308447). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with glutamic acid at codon 476 of the NF1 protein (p.Lys476Glu). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamic acid. |
Laboratory of Medical Genetics, |
RCV001051977 | SCV001548439 | likely pathogenic | Neurofibromatosis, type 1 | 2019-01-01 | no assertion criteria provided | clinical testing |