Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000489112 | SCV000577372 | likely pathogenic | not provided | 2017-04-01 | criteria provided, single submitter | clinical testing | The c.4772+1 G>T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It destroys the canonical splice donor site in intron 35 and leads to abnormal gene splicing; however, the adjacent exon 35 remains in frame. A portion of exon 35 (residues 1555 to 1591) lies within the CRAL-TRIO domain and lipid-binding region. The c.4772+1 G>T variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. In summary, we consider this variant to be likely pathogenic. |
| Labcorp Genetics |
RCV000704356 | SCV000833301 | pathogenic | Neurofibromatosis, type 1 | 2023-05-15 | criteria provided, single submitter | clinical testing | 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: 426827). This variant is also known as c.4835+1G>T. Disruption of this splice site has been observed in individual(s) with neurofibromatosis type 1 (PMID: 29588991; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 35 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. |
| Genome- |
RCV000704356 | SCV002560091 | likely pathogenic | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003470593 | SCV004190738 | pathogenic | Juvenile myelomonocytic leukemia | 2023-05-08 | criteria provided, single submitter | clinical testing |