Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001049663 | SCV001213728 | pathogenic | Neurofibromatosis, type 1 | 2024-06-03 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 33 of the NF1 gene. It does not directly change the encoded amino acid sequence of the NF1 protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). 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: 846370). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 33, but is expected to preserve the integrity of the reading-frame (Invitae). This variant disrupts a region of the NF1 protein in which other variant(s) (p.Gly1498Glu) have been determined to be pathogenic (PMID: 26635368). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Greenwood Genetic Center Diagnostic Laboratories, |
RCV003117724 | SCV003799146 | uncertain significance | not provided | 2022-11-01 | criteria provided, single submitter | clinical testing | PP3_Moderate, PM2 |