Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Human Genetics, |
RCV000660021 | SCV000781963 | pathogenic | Neurofibromatosis, type 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Clinical Molecular Genetics Laboratory, |
RCV000660021 | SCV000897649 | pathogenic | Neurofibromatosis, type 1 | 2019-04-02 | criteria provided, single submitter | clinical testing | |
3billion | RCV001775145 | SCV002011926 | pathogenic | Neurofibromatosis-Noonan syndrome | 2021-10-02 | criteria provided, single submitter | clinical testing | Canonical splice site: predicted to alter splicing and result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is not observed in the gnomAD v2.1.1 dataset (PM2). The variant has been reported multiple times as an established pathogenic variant (ClinVar ID: VCV000547617.2). Patient's phenotype is considered compatible with Neurofibromatosis-Noonan syndrome (3billion dataset, PP4). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline |
Invitae | RCV000660021 | SCV002117451 | pathogenic | Neurofibromatosis, type 1 | 2022-05-08 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 21 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 clinical features of neurofibromatosis type 1 (PMID: 16944272, 18546366, 27999334, 31370276). ClinVar contains an entry for this variant (Variation ID: 547617). 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- |
RCV000660021 | SCV002561807 | pathogenic | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing |