Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000606706 | SCV000731805 | uncertain significance | not specified | 2017-07-20 | criteria provided, single submitter | clinical testing | The p.Ile1827Met variant in NF1 has not been previously reported in individuals with RASopathy or in large population studies. Computational prediction tools an d conservation analysis do not provide strong support for or against an impact t o the protein. In summary, the clinical significance of the p.Ile1827Met variant is uncertain. |
| Labcorp Genetics |
RCV000700096 | SCV000828837 | uncertain significance | Neurofibromatosis, type 1 | 2024-01-04 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1806 of the NF1 protein (p.Ile1806Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of NF1-related conditions (PMID: 32107864). This variant is also known as c.5481C>G (p.Ile1827Met). ClinVar contains an entry for this variant (Variation ID: 517503). 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 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. |
| Genome- |
RCV000700096 | SCV002560876 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002343166 | SCV002649334 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2021-03-31 | criteria provided, single submitter | clinical testing | The p.I1806M variant (also known as c.5418C>G), located in coding exon 37 of the NF1 gene, results from a C to G substitution at nucleotide position 5418. The isoleucine at codon 1806 is replaced by methionine, an amino acid with highly similar properties. This alteration, designated c.5481C>G p.(Ile1827Met), was detected in 1/28 patients with either NeurofibromatosisNoonan syndrome or a suspicion of Noonan spectrum disorders and caféaulait spots with a prior negative Noonan spectrum disorder panel testing, and was classified as a variant of unknown significance by the authors (Witkowski L et al. Mol Genet Genomic Med, 2020 04;8:e1180). 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. |