Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000479978 | SCV000567428 | pathogenic | not provided | 2015-08-13 | criteria provided, single submitter | clinical testing | The Q1188P substitution in the NF1 gene has not been reported previously as a pathogenic variant noras a benign polymorphism, to our knowledge. The Q1188P variant was not observed in approximately6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project,indicating it is not a common benign variant in these populations. The Q1188P variant is a non-conservativeamino acid substitution, which is likely to impact secondary protein structure as these residues differ inpolarity, charge, size and/or other properties. This substitution occurs at a position that is conserved acrossspecies. In silico analysis predicts this variant is probably damaging to the protein structure/function.Missense variants in nearby residues (L1183R, L1187P, Q1189R, G1190S, T1191K, T1191R, andF1193C) have been reported in the Human Gene Mutation Database in association with neurofibromatosistype 1 (Stenson et al., 2014), supporting the functional importance of this region of the protein. Weinterpret Q1188P as a pathogenic variant. |
| Labcorp Genetics |
RCV005090936 | SCV005733653 | uncertain significance | Neurofibromatosis, type 1 | 2024-12-09 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 1188 of the NF1 protein (p.Gln1188Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 419549). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt NF1 protein function with a positive predictive value of 95%. 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. |