Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000167453 | SCV000218309 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-12-23 | criteria provided, single submitter | clinical testing | Thep.F71Svariant (also known as c.212T>C), located in codingexon3 of theNF1gene, results from a T to C substitution at nucleotide position 212. Thephenylalanineatcodon71 is replaced byserine, an amino acid with highly dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6501 samples (13002 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 110000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species; however, serineis the reference amino acid in one reptile species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of p.F71S remains unclear. |
| Invitae | RCV000794104 | SCV000933493 | uncertain significance | Neurofibromatosis, type 1 | 2023-12-27 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 71 of the NF1 protein (p.Phe71Ser). This variant is present in population databases (rs752396270, gnomAD 0.0009%). 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: 187703). 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 not expected to disrupt NF1 protein function with a negative 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- |
RCV000794104 | SCV002561420 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002498829 | SCV002791504 | uncertain significance | Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis | 2021-12-02 | criteria provided, single submitter | clinical testing |