Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000003453 | SCV000553677 | pathogenic | Neurofibromatosis, type 2 | 2023-07-28 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg341*) in the NF2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NF2 are known to be pathogenic (PMID: 9643284, 16983642). 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 2 (PMID: 7913580, 8379998, 11809806, 12566519, 21671232). ClinVar contains an entry for this variant (Variation ID: 3292). For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV000497720 | SCV000589606 | pathogenic | not provided | 2023-03-07 | 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 at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 11809806, 15609345, 25525159, 8379998, 19234911, 9643284, 29130639, 12566519, 21671232, 7913580, 10790209, 7717450, 16630136, 30325044, 31273341, 32724039, 16983642, 33067351, 19249154) |
Center for Human Genetics, |
RCV000003453 | SCV000782126 | pathogenic | Neurofibromatosis, type 2 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000003453 | SCV002045425 | pathogenic | Neurofibromatosis, type 2 | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003278654 | SCV004007056 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-06-13 | criteria provided, single submitter | clinical testing | The p.R341* pathogenic mutation (also known as c.1021C>T), located in coding exon 11 of the NF2 gene, results from a C to T substitution at nucleotide position 1021. This changes the amino acid from an arginine to a stop codon within coding exon 11. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration has been observed in at least one individual with a personal and/or family history that is consistent with NF2-related disease (Ambry internal data). This mutation has been identified in multiple patients meeting diagnostic criteria for neurofibromatosis type 2 (Walter J et al. Clin Neurol Neurosurg, 2009 Jun;111:454-9; Pemov A et al. Sci Rep, 2020 Jul;10:12563). 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. |
OMIM | RCV000003453 | SCV000023611 | pathogenic | Neurofibromatosis, type 2 | 1994-08-01 | no assertion criteria provided | literature only |