Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Human Genetics, |
RCV000659969 | SCV000781881 | pathogenic | Neurofibromatosis, type 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000659969 | SCV000960450 | pathogenic | Neurofibromatosis, type 1 | 2023-08-25 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 8 of the NF1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in the gain of 20 amino acid residue(s), but is expected to preserve the integrity of the reading-frame. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with neurofibromatosis type1 (PMID: 10712197, 28961165, 30530636; Invitae). ClinVar contains an entry for this variant (Variation ID: 547573). Studies have shown that disruption of this splice site results in the activation of a cryptic splice site in intron 8 (PMID: 18546366; Invitae). For these reasons, this variant has been classified as Pathogenic. |
Genome- |
RCV000659969 | SCV002561608 | pathogenic | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002442381 | SCV002682985 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-03-16 | criteria provided, single submitter | clinical testing | The c.888+1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide after coding exon 8 of the NF1 gene. The mutation has been detected in multiple unrelated individuals diagnosed with or suspected of having neurofibromatosis type 1 (NF1) (Fahsold R et al. Am. J. Hum. Genet., 2000 Mar;66:790-818; Ars E et al. J. Med. Genet., 2003 Jun;40:e82; Pros E et al. Hum. Mutat., 2008 Sep;29:E173-93; Frayling IM et al. J. Med. Genet., 2019 04;56:209-219). This mutation was also reported to result in either skipping of exon 8 or activation of a cryptic donor site in intron 8 (Ars E et al. J. Med. Genet., 2003 Jun;40:e82; Pros E et al. Hum. Mutat., 2008 Sep;29:E173-93; Frayling IM et al. J. Med. Genet., 2019 04;56:209-219; Ambry internal data). Furthermore, other variants at the same donor site (c.888+1G>C and c.888+2T>G) have been identified in individuals diagnosed with or suspected of having NF1 (Pasmant E et al. Mol. Med. 2011 Sep;17:79-87; Bonatti F et al. Int J Mol Sci, 2017 Sep;18:). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
Gene |
RCV004702263 | SCV005202028 | pathogenic | not provided | 2024-02-09 | criteria provided, single submitter | clinical testing | Canonical splice site variant demonstrated to result in abnormal gene splicing in a gene for which loss-of-function is a known mechanism of disease (PMID: 16741618, 18546366, 23913538, 30530636); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 30530636, 16741618, 23913538, 10712197, 18546366, 31201679) |