Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000166659 | SCV000217464 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-08-11 | criteria provided, single submitter | clinical testing | The p.S2496C variant (also known as c.7487C>G), located in coding exon 51 of the NF1 gene, results from a C to G substitution at nucleotide position 7487. The serine at codon 2496 is replaced by cysteine, an amino acid with dissimilar properties. This variant was previously reported in the SNPDatabase as rs371773406. Based on data from the NHLBI Exome Sequencing Project (ESP), the G allele has an overall frequency of approximately 0.01% (1/13006) total alleles studied, having been observed in 0.02% (1/4406) African American alleles. To date, this alteration has been detected with an allele frequency of approximately 0.004% (greater than 55000 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 possibly damaging and deleterious by PolyPhen and SIFT in silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of p.S2496C remains unclear. |
Invitae | RCV000198334 | SCV000254513 | uncertain significance | Neurofibromatosis, type 1 | 2024-01-26 | 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 2475 of the NF1 protein (p.Ser2475Cys). This variant is present in population databases (rs371773406, gnomAD 0.007%). 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: 186986). 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 with a positive predictive value of 80%. 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- |
RCV000198334 | SCV002561089 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Gene |
RCV002460944 | SCV002756760 | uncertain significance | not provided | 2022-11-21 | 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; This variant is associated with the following publications: (PMID: 25486365) |
Fulgent Genetics, |
RCV002492671 | SCV002785411 | uncertain significance | Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis | 2022-01-25 | criteria provided, single submitter | clinical testing |