Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Human Genetics, |
RCV000660050 | SCV000782010 | likely pathogenic | Neurofibromatosis, type 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000660050 | SCV001209283 | pathogenic | Neurofibromatosis, type 1 | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln1374*) 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 1 (PMID: 23624750, 27838393). ClinVar contains an entry for this variant (Variation ID: 547641). For these reasons, this variant has been classified as Pathogenic. |
Genome- |
RCV000660050 | SCV002560026 | pathogenic | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003163041 | SCV003893750 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-12-08 | criteria provided, single submitter | clinical testing | The p.Q1374* pathogenic mutation (also known as c.4120C>T), located in coding exon 31 of the NF1 gene, results from a C to T substitution at nucleotide position 4120. This changes the amino acid from a glutamine to a stop codon within coding exon 31. This alteration has been identified in individuals with a clinical diagnosis of neurofibromatosis type 1 (Ambry internal data; Campos B et al. Breast Cancer Res Treat, 2013 Jun;139:597-602). 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. |