Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002317167 | SCV000666835 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2021-06-16 | criteria provided, single submitter | clinical testing | The p.L1418M variant (also known as c.4252T>A), located in coding exon 31 of the NF1 gene, results from a T to A substitution at nucleotide position 4252. The leucine at codon 1418 is replaced by methionine, 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. |
| Gene |
RCV002291672 | SCV002584417 | uncertain significance | not provided | 2022-04-14 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 22807134, 25486365) |
| Fulgent Genetics, |
RCV002476231 | SCV002784580 | uncertain significance | Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis | 2021-09-27 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV002526834 | SCV003452744 | uncertain significance | Neurofibromatosis, type 1 | 2022-02-24 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 481992). This variant has not been reported in the literature in individuals affected with NF1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1418 of the NF1 protein (p.Leu1418Met). |