Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000216551 | SCV000276155 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-06-02 | criteria provided, single submitter | clinical testing | The p.N67S variant (also known as c.200A>G), located in coding exon 2 of the NF1 gene, results from an A to G substitution at nucleotide position 200. The asparagine at codon 67 is replaced by serine, an amino acid with highly similar properties. This variant was previously reported in the SNPDatabase as rs375038808. Based on data from the NHLBI Exome Sequencing Project (ESP), the G allele has an overall frequency of approximately 0.02% (2/13006) total alleles studied, having been observed in0.02% (2/8600) European American alleles.This variant was not reported in the 1000 Genomes Project population-based cohort. 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 well 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.N67Sremains unclear. |
Center for Human Genetics, |
RCV000659957 | SCV000781863 | uncertain significance | Neurofibromatosis, type 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000659957 | SCV001570119 | uncertain significance | Neurofibromatosis, type 1 | 2023-12-20 | 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 67 of the NF1 protein (p.Asn67Ser). This variant is present in population databases (rs375038808, gnomAD 0.003%). 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: 232106). 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- |
RCV000659957 | SCV002561418 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Gene |
RCV003441799 | SCV004170240 | uncertain significance | not provided | 2023-10-10 | criteria provided, single submitter | clinical testing | 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 |
Baylor Genetics | RCV003462487 | SCV004198288 | uncertain significance | Juvenile myelomonocytic leukemia | 2023-09-29 | criteria provided, single submitter | clinical testing |