Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000632345 | SCV000753523 | pathogenic | Neurofibromatosis, type 1 | 2022-02-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Studies have shown that this premature translational stop signal alters NF1 gene expression (PMID: 25788518). ClinVar contains an entry for this variant (Variation ID: 527470). This variant is also known as c.240_241delTC. This premature translational stop signal has been observed in individual(s) with neurofibromatosis type 1 (PMID: 16944272, 18546366, 23758643). This variant is present in population databases (rs771115661, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Gln83Valfs*23) 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). |
Center for Human Genetics, |
RCV000632345 | SCV000781867 | pathogenic | Neurofibromatosis, type 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000632345 | SCV002561561 | pathogenic | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002458005 | SCV002738204 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-04-21 | criteria provided, single submitter | clinical testing | The c.246_247delTC pathogenic mutation, located in coding exon 3 of the NF1 gene, results from a deletion of two nucleotides at nucleotide positions 246 to 247, causing a translational frameshift with a predicted alternate stop codon (p.Q83Vfs*23). This alteration was identified in two separate cohorts undergoing genetic testing due to a diagnosis or clinical suspicion of neurofibromatosis type 1 (Pros E et al. Hum Mutat, 2008 Sep;29:E173-93; Bolcekova A et al. Neoplasma, 2013;60:655-65). 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. |