Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000204501 | SCV000259286 | uncertain significance | Neurofibromatosis, type 1 | 2024-01-10 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1375 of the NF1 protein (p.Arg1375His). This variant is present in population databases (rs368685980, gnomAD 0.002%). 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: 219424). 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. |
| Ambry Genetics | RCV002317729 | SCV000670302 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-11-22 | criteria provided, single submitter | clinical testing | The p.R1375H variant (also known as c.4124G>A), located in coding exon 31 of the NF1 gene, results from a G to A substitution at nucleotide position 4124. The arginine at codon 1375 is replaced by histidine, 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. |
| Genome- |
RCV000204501 | SCV002560387 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002485335 | SCV002793905 | uncertain significance | Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis | 2022-05-06 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV003884404 | SCV004702856 | uncertain significance | not provided | 2024-02-01 | criteria provided, single submitter | clinical testing | NF1: PM2, PP3 |