Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002317178 | SCV000670313 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-10-12 | criteria provided, single submitter | clinical testing | The p.S1889C variant (also known as c.5666C>G), located in coding exon 38 of the NF1 gene, results from a C to G substitution at nucleotide position 5666. The serine at codon 1889 is replaced by cysteine, an amino acid with dissimilar properties. In a Japanese male breast cancer cohort, this variant was seen in 0/53 cases and 2/12490 controls (Momozawa Y et al. Nat Commun. 2018 10;9(1):4083). 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. |
| Invitae | RCV000632443 | SCV000753624 | uncertain significance | Neurofibromatosis, type 1 | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1889 of the NF1 protein (p.Ser1889Cys). This variant is present in population databases (rs751904277, 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: 484003). 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. |
| Fulgent Genetics, |
RCV000764114 | SCV000895082 | 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 | |
| Genome- |
RCV000632443 | SCV002560903 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV003159137 | SCV003852972 | uncertain significance | not provided | 2023-03-30 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 30287823) |
| Genetics and Molecular Pathology, |
RCV000632443 | SCV004175537 | uncertain significance | Neurofibromatosis, type 1 | 2023-08-03 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003459363 | SCV004198284 | uncertain significance | Juvenile myelomonocytic leukemia | 2023-10-01 | criteria provided, single submitter | clinical testing |