Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001044247 | SCV001208034 | uncertain significance | Neurofibromatosis, type 1 | 2022-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 546 of the NF1 protein (p.Met546Val). 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: 841928). 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. 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. |
| Gene |
RCV001759756 | SCV002007289 | uncertain significance | not provided | 2024-06-04 | criteria provided, single submitter | clinical testing | 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; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25486365) |
| Genome- |
RCV001044247 | SCV002561931 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002400252 | SCV002707643 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2018-09-10 | criteria provided, single submitter | clinical testing | The p.M546V variant (also known as c.1636A>G), located in coding exon 14 of the NF1 gene, results from an A to G substitution at nucleotide position 1636. The methionine at codon 546 is replaced by valine, an amino acid with highly 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003461464 | SCV004198327 | uncertain significance | Juvenile myelomonocytic leukemia | 2023-09-06 | criteria provided, single submitter | clinical testing |