Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000704291 | SCV000833234 | uncertain significance | Neurofibromatosis, type 1 | 2023-09-05 | criteria provided, single submitter | clinical testing | 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) has been performed at Invitae 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. ClinVar contains an entry for this variant (Variation ID: 580678). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 2316 of the NF1 protein (p.Leu2316Phe). This variant is present in population databases (rs367734104, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with NF1-related conditions. |
Ambry Genetics | RCV002388334 | SCV001188097 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2019-11-20 | criteria provided, single submitter | clinical testing | The p.L2316F variant (also known as c.6946C>T), located in coding exon 46 of the NF1 gene, results from a C to T substitution at nucleotide position 6946. The leucine at codon 2316 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Genome- |
RCV000704291 | SCV002561025 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002485756 | SCV002790838 | uncertain significance | Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis | 2022-03-06 | criteria provided, single submitter | clinical testing |