Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001216938 | SCV001388760 | pathogenic | Neurofibromatosis, type 1 | 2021-03-29 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp1236*) 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 (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This nonsense change has been observed in individual(s) with neurofibromatosis type 1 (NF1) (PMID: 10712197). ClinVar contains an entry for this variant (Variation ID: 946140). |
| Ce |
RCV002292617 | SCV002585632 | pathogenic | not provided | 2022-08-01 | criteria provided, single submitter | clinical testing | NF1: PVS1, PM2 |
| Ambry Genetics | RCV002348724 | SCV002621347 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2021-12-10 | criteria provided, single submitter | clinical testing | The p.W1236* pathogenic mutation (also known as c.3708G>A), located in coding exon 27 of the NF1 gene, results from a G to A substitution at nucleotide position 3708. This changes the amino acid from a tryptophan to a stop codon within coding exon 27. This change occurs in the last base pair of coding exon 27, which makes it possible to have some effect on normal mRNA splicing. In silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice donor site. In addition, another alteration resulting in the same premature stop codon p.W1236* (c.3707G>A) has been identified in individuals with NF1 (Fahsold R et al. Am J Hum Genet 2000 Mar;66(3):790-818; Stella A et al. Genes (Basel) 2018 Apr;9(4). 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. |