Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001382573 | SCV001581413 | pathogenic | Neurofibromatosis, type 1 | 2020-05-29 | criteria provided, single submitter | clinical testing | Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with neurofibromatosis, type 1 (PMID: 31730495). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg1413*) in the NF1 gene. It is expected to result in an absent or disrupted protein product. |
| Ambry Genetics | RCV002329403 | SCV002630462 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2021-08-19 | criteria provided, single submitter | clinical testing | The p.R1413* pathogenic mutation (also known as c.4237A>T), located in coding exon 31 of the NF1 gene, results from an A to T substitution at nucleotide position 4237. This changes the amino acid from an arginine to a stop codon within coding exon 31. This alteration has been observed in at least one individual with a personal and/or family history that is consistent with Neurofibromatosis type 1-related disease (Ambry internal data). This alteration was identified in 1 of 138 patients clinically diagnosed with Neurofibromatosis type 1 (Assunto A et al. Orphanet J Rare Dis, 2019 11;14:261). 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. |