Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000817442 | SCV000958002 | pathogenic | Neurofibromatosis, type 1 | 2023-09-29 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 9 of the NF1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 660278). Disruption of this splice site has been observed in individuals with neurofibromatosis type 1 (PMID: 12807981, 17426081, 23913538, 24413922). This variant is not present in population databases (gnomAD no frequency). |
3billion | RCV000817442 | SCV003841312 | pathogenic | Neurofibromatosis, type 1 | 2023-02-23 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. This variant was predicted to alter splicing and result in a loss or disruption of normal protein function. Multiple pathogenic loss-of-function variants are reported downstream of the variant. The variant has been reported to be associated with NF1 related disorder (ClinVar ID: VCV000660278 / PMID: 12807981). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. |
Gene |
RCV003328633 | SCV004035781 | likely pathogenic | not provided | 2023-03-15 | criteria provided, single submitter | clinical testing | Canonical splice site variant shown to result in skipping of the in-frame exon 9 in patient-derived samples (Ars et al., 2003; Pros et al., 2008); Observed in an individual with features of neurofibromatosis type 1 (Ars et al., 2003); Not observed at significant frequency in large population cohorts (gnomAD); Deletions involving coding exons of this gene are a known mechanism of disease (HGMD; other references); Also known as IVS7+1G>A; This variant is associated with the following publications: (PMID: 25525159, 10712197, 24413922, 23913538, 26076063, 12807981, 18546366, 17426081) |
Baylor Genetics | RCV003461247 | SCV004198324 | pathogenic | Juvenile myelomonocytic leukemia | 2023-09-06 | criteria provided, single submitter | clinical testing |