Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001070068 | SCV001235277 | pathogenic | Neurofibromatosis, type 1 | 2021-06-30 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Leu898 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21512413, 29415745, 9150739, 29685074, 20605257, 24676943). This suggests that this residue is clinically-significant, and that variants that disrupt this residue are likely to be disease-causing. 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 clinical features of neurofibromatosis type I (Invitae). ClinVar contains an entry for this variant (Variation ID: 863165). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with arginine at codon 898 of the NF1 protein (p.Leu898Arg). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and arginine. |