Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000199054 | SCV000254502 | uncertain significance | Neurofibromatosis, type 1 | 2024-01-27 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 1540 of the NF1 protein (p.Ser1540Asn). This variant is present in population databases (rs751414513, gnomAD 0.002%). 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: 216404). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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. |
Ambry Genetics | RCV000563776 | SCV000662763 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-01-14 | criteria provided, single submitter | clinical testing | Thep.S1561Nvariant (also known as c.4682G>A)located in coding exon 35 of theNF1gene, results from a G to A substitution at nucleotide position 4682. The serine at codon 1561 is replaced by asparagine, 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 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.003% (greater than 110000 alleles 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.S1561N remains unclear. |
Mendelics | RCV000199054 | SCV000839150 | uncertain significance | Neurofibromatosis, type 1 | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001577944 | SCV001805442 | likely benign | not provided | 2021-02-24 | criteria provided, single submitter | clinical testing | In silico analysis supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Sema4, |
RCV000563776 | SCV002527581 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-22 | criteria provided, single submitter | curation |