Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001232364 | SCV001404920 | uncertain significance | Neurofibromatosis, type 1 | 2023-09-29 | 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. Studies have shown this variant is associated with activation of a cryptic splice site, but one or more of the resulting mRNA isoform(s) may be naturally occurring (Invitae). ClinVar contains an entry for this variant (Variation ID: 959080). 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 affects codon 1505 of the NF1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the NF1 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. |
| Ambry Genetics | RCV002339636 | SCV002635150 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-03-13 | criteria provided, single submitter | clinical testing | The c.4515G>A variant (also known as p.R1505R), located in coding exon 34 of the NF1 gene, results from a G to A substitution at nucleotide position 4515. This variant impacts the first base pair of coding exon 34.This nucleotide substitution does not change the amino acid at codon 1505. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may weaken the native splice acceptor site; however, direct evidence is insufficient at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |