Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Human Genetics, |
RCV000660038 | SCV000781990 | likely pathogenic | Neurofibromatosis, type 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000660038 | SCV000958325 | pathogenic | Neurofibromatosis, type 1 | 2023-02-09 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1196 of the NF1 protein (p.Leu1196Val). 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. ClinVar contains an entry for this variant (Variation ID: 547629). This missense change has been observed in individual(s) with neurofibromatosis type 1 (PMID: 26740943; Invitae). This variant is not present in population databases (gnomAD no frequency). This variant disrupts the p.Leu1196 amino acid residue in NF1. Other variant(s) that disrupt this residue have been observed in individuals with NF1-related conditions (PMID: 15060124, 17103458, 22664660, 23047742, 27838393), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV003163040 | SCV003915398 | likely pathogenic | not provided | 2022-10-28 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in a cohort of individuals with clinical characteristics of neurofibromatosis type 1 (Bianchessi et al., 2015); This variant is associated with the following publications: (PMID: 25486365, 22807134, 2121369, 26740943) |