Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000694562 | SCV000823013 | pathogenic | Neurofibromatosis, type 1 | 2025-01-13 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp1641*) 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 I (PMID: 18041031, 23222849, 26478990). This variant is also known as p.W1662*. ClinVar contains an entry for this variant (Variation ID: 573015). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV004559614 | SCV005048268 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-10-05 | criteria provided, single submitter | clinical testing | The p.W1641* pathogenic mutation (also known as c.4922G>A), located in coding exon 36 of the NF1 gene, results from a G to A substitution at nucleotide position 4922. This changes the amino acid from a tryptophan to a stop codon within coding exon 36. This alteration has been observed in multiple individuals with a personal and/or family history that is consistent with NF1-related disease (Brinckmann A et al. Electrophoresis, 2007 Dec;28:4295-301; Esposito T et al. J Neurochem, 2015 Dec;135:1123-8; Giugliano T et al. Genes (Basel), 2019 Jul;10; Napolitano F et al. Genes (Basel), 2022 Jun;13; Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |
| Gene |
RCV004702336 | SCV005202052 | pathogenic | not provided | 2023-10-27 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 28955729, 26478990, 23222849, 24676424, 33877690, 18041031, 31370276, 33372952, 34233200) |
| Fulgent Genetics, |
RCV005021071 | SCV005646768 | pathogenic | Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis | 2024-01-24 | criteria provided, single submitter | clinical testing | |
| Human Genome Sequencing Center Clinical Lab, |
RCV001257530 | SCV001434356 | pathogenic | Rhabdomyosarcoma | 2020-09-01 | no assertion criteria provided | provider interpretation |