Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001224377 | SCV001396567 | pathogenic | Neurofibromatosis, type 1 | 2024-09-14 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp777*) 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 clinical features of NF1-related conditions (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 952296). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV004557450 | SCV005047551 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-11-16 | criteria provided, single submitter | clinical testing | The p.W777* pathogenic mutation (also known as c.2330G>A), located in coding exon 20 of the NF1 gene, results from a G to A substitution at nucleotide position 2330. This changes the amino acid from a tryptophan to a stop codon within coding exon 20. This alteration has been observed in multiple individuals with a personal and/or family history that is consistent with NF1-related disease (van Minkelen R et al. Clin Genet, 2014 Apr;85:318-27; D'Angelo F et al. Nat Med, 2019 Jan;25:176-187; Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |
| St. |
RCV001224377 | SCV005689167 | pathogenic | Neurofibromatosis, type 1 | 2024-11-20 | criteria provided, single submitter | clinical testing | The NF1 c.2330G>A (p.Trp777Ter) change is a nonsense variant that is predicted to cause premature protein truncation or absence of the protein due to nonsense mediated decay. This variant has been observed in individuals with Neurofibromatosis type 1 (PMID: 30531922, LOVD database). This variant is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). Loss-of-function variants in NF1 are known to be pathogenic (PMID: 9003501, 10712197). In summary, this variant meets criteria to be classified as pathogenic. |