Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000632429 | SCV000753609 | pathogenic | Neurofibromatosis, type 1 | 2022-10-20 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with neurofibromatosis, type 1 (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1422 of the NF1 protein (p.Ser1422Leu). ClinVar contains an entry for this variant (Variation ID: 527535). 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. |
| Mendelics | RCV000632429 | SCV000839148 | uncertain significance | Neurofibromatosis, type 1 | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001540502 | SCV001758393 | pathogenic | not provided | 2024-09-10 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate reduction in RAS GAP activity and protein expression similar to wildtype (Douben H et al. (2023) Hindawi Human Mutation. 2023 (Article ID 9628049):1-14); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21520333, 23656349, 36251260, 35264596, Douben2023[Functional study], 25486365, 22807134) |
| Ambry Genetics | RCV002331121 | SCV002629944 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-03-10 | criteria provided, single submitter | clinical testing | The p.S1422L variant (also known as c.4265C>T), located in coding exon 31 of the NF1 gene, results from a C to T substitution at nucleotide position 4265. The serine at codon 1422 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |