Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000215696 | SCV000277623 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-08-06 | criteria provided, single submitter | clinical testing | The p.N2602D variant (also known as c.7804A>G), located in coding exon 53 of the NF1 gene, results from an A to G substitution at nucleotide position 7804. The asparagine at codon 2602 is replaced by aspartic acid, an amino acid with highly similar properties. This variant was previously reported in the SNPDatabase as rs150657839. 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 in0.01% (1/8600) 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 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.N2602Dremains unclear. |
| Labcorp Genetics |
RCV001854688 | SCV002158934 | uncertain significance | Neurofibromatosis, type 1 | 2022-08-23 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 233280). This variant has not been reported in the literature in individuals affected with NF1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 2581 of the NF1 protein (p.Asn2581Asp). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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- |
RCV001854688 | SCV002561134 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004558563 | SCV005048555 | likely benign | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2024-11-20 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Fulgent Genetics, |
RCV005008169 | SCV005639973 | uncertain significance | Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis | 2024-02-24 | criteria provided, single submitter | clinical testing |