Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000222862 | SCV000275839 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-05-15 | criteria provided, single submitter | clinical testing | The p.S1164A variant (also known as c.3490T>G), located in coding exon 26 of the NF1 gene, results from a T to G substitution at nucleotide position 3490. The serine at codon 1164 is replaced by alanine, an amino acid with 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 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 55000alleles tested) in our clinical cohort.This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis.Since supporting evidence is limited at this time, the clinical significance of p.S1164Aremains unclear. |
| Invitae | RCV000543603 | SCV000628525 | uncertain significance | Neurofibromatosis, type 1 | 2023-07-09 | criteria provided, single submitter | clinical testing | 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. 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. This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 1164 of the NF1 protein (p.Ser1164Ala). This variant is present in population databases (rs750303863, 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: 231861). |
| Genome- |
RCV000543603 | SCV002560301 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002494595 | SCV002782822 | uncertain significance | Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis | 2021-10-12 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV003325471 | SCV004032035 | uncertain significance | not provided | 2023-03-02 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 30274822, 25486365, 2121369, 22807134) |
| Baylor Genetics | RCV003469043 | SCV004190705 | uncertain significance | Juvenile myelomonocytic leukemia | 2023-05-30 | criteria provided, single submitter | clinical testing |