Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000794540 | SCV000933954 | uncertain significance | Neurofibromatosis, type 1 | 2024-07-03 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 2629 of the NF1 protein (p.Phe2629Cys). This variant is present in population databases (rs754443238, gnomAD 0.007%). 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: 641323). 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 | RCV003166119 | SCV003854945 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-12-19 | criteria provided, single submitter | clinical testing | The p.F2629C variant (also known as c.7886T>G), located in coding exon 53 of the NF1 gene, results from a T to G substitution at nucleotide position 7886. The phenylalanine at codon 2629 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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. |
Fulgent Genetics, |
RCV005021197 | SCV005639980 | uncertain significance | Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis | 2024-05-17 | criteria provided, single submitter | clinical testing |