Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001217579 | SCV001389425 | pathogenic | Neurofibromatosis, type 1 | 2023-12-31 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln2117*) in the NF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Neurofibromatosis type 1 and breast cancer (PMID: 28529006, 30530636). ClinVar contains an entry for this variant (Variation ID: 946672). Studies have shown that this premature translational stop signal is associated with inconclusive levels of altered splicing (Invitae). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002365983 | SCV002657299 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2018-12-26 | criteria provided, single submitter | clinical testing | The p.Q2117* pathogenic mutation (also known as c.6349C>T), located in coding exon 41 of the NF1 gene, results from a C to T substitution at nucleotide position 6349. This changes the amino acid from a glutamine to a stop codon within coding exon 41. This mutation was previously described in an individual with clinical and molecular diagnosis of neurofibromatosis type 1 (Paulo P et al. J Mol Diagn, 2017 07;19:502-513). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |