Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000165332 | SCV000216055 | uncertain significance | Hereditary cancer-predisposing syndrome | 2014-08-20 | criteria provided, single submitter | clinical testing | The p.N1465S variant (also known as c.4394A>G), located in coding exon 33 of the NF1 gene, results from an A to G substitution at nucleotide position 4394. The asparagine at codon 1465 is replaced by serine, an amino acid with highly similar 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 6500 samples (13000 alleles) with coverage at this position.<span style="background-color: initial;">To date, this alteration has been detected with an allele frequency of approximately 0.01% (greater than 11000 alleles tested) in our clinical cohort. Based on protein sequence alignment, this<span style="background-color: initial;">amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be benign and deleterious by PolyPhen and SIFT <em style="background-color: initial;">in silico<span style="background-color: initial;"> analyses, respectively.<span style="background-color: initial;">Since supporting evidence is limited at this time, the clinical significance of p.N1465S remains unclear. |
| Fulgent Genetics, |
RCV000764111 | SCV000895079 | uncertain significance | Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001222970 | SCV001395096 | uncertain significance | Neurofibromatosis, type 1 | 2023-09-06 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1444 of the NF1 protein (p.Asn1444Ser). This variant is not present in population databases (gnomAD no frequency). 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: 185835). 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. 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- |
RCV001222970 | SCV002560419 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Genome |
RCV003483537 | SCV004228820 | not provided | Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis | no assertion provided | phenotyping only | Variant interpreted as Uncertain significance and reported on 11-09-2020 by Lab Invitae. This variant was reported as possibly mosaic in this individual. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. |