Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000795559 | SCV000935025 | uncertain significance | Neurofibromatosis, type 1 | 2025-02-02 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 326 of the NF1 protein (p.Lys326Glu). 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: 642154). 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. |
| Ambry Genetics | RCV002386394 | SCV002695430 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2024-08-21 | criteria provided, single submitter | clinical testing | The p.K326E variant (also known as c.976A>G), located in coding exon 9 of the NF1 gene, results from an A to G substitution at nucleotide position 976. The lysine at codon 326 is replaced by glutamic acid, an amino acid with similar 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. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Prevention |
RCV004549871 | SCV004712557 | uncertain significance | NF1-related disorder | 2023-11-11 | no assertion criteria provided | clinical testing | The NF1 c.976A>G variant is predicted to result in the amino acid substitution p.Lys326Glu. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/642154/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |