Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000578644 | SCV000680719 | pathogenic | not provided | 2017-12-27 | criteria provided, single submitter | clinical testing | The c.2002-1G>A splice site variant in the NF1 gene has been previously reported in at least one individual with a clinical diagnosis of neurofibromatosis type 1 (Griffiths et al., 2007). This pathogenic variant destroys the canonical splice acceptor site in intron 17, and is expected to cause abnormal gene splicing. The c.2002-1G>A variant is not observed in large population cohorts (Lek et al., 2016). Based on currently available evidence, we consider c.2002-1G>A to be pathogenic. |
Center for Human Genetics, |
RCV000660002 | SCV000781934 | pathogenic | Neurofibromatosis, type 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000660002 | SCV000827499 | pathogenic | Neurofibromatosis, type 1 | 2023-11-01 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 17 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). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with NF1-related conditions (PMID: 16944272, 31370276). ClinVar contains an entry for this variant (Variation ID: 488815). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Genome- |
RCV000660002 | SCV002561724 | pathogenic | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing |