Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002315707 | SCV000663124 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2024-01-05 | criteria provided, single submitter | clinical testing | The p.G2241W variant (also known as c.6721G>T), located in coding exon 44 of the NF1 gene, results from a G to T substitution at nucleotide position 6721. The glycine at codon 2241 is replaced by tryptophan, an amino acid with highly 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. |
| Labcorp Genetics |
RCV000694164 | SCV000822595 | uncertain significance | Neurofibromatosis, type 1 | 2024-12-29 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 2241 of the NF1 protein (p.Gly2241Trp). This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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: 480114). 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) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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. |
| Genome- |
RCV000694164 | SCV002560998 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV002466536 | SCV002761971 | uncertain significance | not provided | 2022-11-29 | criteria provided, single submitter | clinical testing | 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 |
| Fulgent Genetics, |
RCV005010537 | SCV005639942 | uncertain significance | Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis | 2024-03-06 | criteria provided, single submitter | clinical testing |