ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.2991-1G>C

dbSNP: rs1060500273
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000538864 SCV000628476 pathogenic Neurofibromatosis, type 1 2022-02-28 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 22 of the NF1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with neurofibromatosis type 1 (NF1), neurofibromatosis-Noonan syndrome and sporadic pheochromocytoma and additional features consistent with NF1 (PMID: 8829638, 10712197, 22962301, 23913538, 24357598). ClinVar contains an entry for this variant (Variation ID: 457613). Studies have shown that disruption of this splice site results in skipping of exon 23 (also known as exon 18 in the literature), but is expected to preserve the integrity of the reading-frame (PMID: 10712197). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002497070 SCV002807157 pathogenic Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis 2021-10-24 criteria provided, single submitter clinical testing
GeneDx RCV003318586 SCV004022945 pathogenic not provided 2023-07-24 criteria provided, single submitter clinical testing Intronic variant predicted to result in an in-frame deletion of exon 23 which contains the GTPase activating protein domain and has been confirmed via RT-PCR (Xu et al., 1990; Fahsold et al., 2000; Luo et al., 2014); Observed in individuals with suspected or clinical diagnosed neurofibromatosis type 1 referred for genetic testing at GeneDx and in published literature (Fahsold et al., 2000; Burnichon et al., 2012; Kang et al., 2020); Deletions involving coding exons of this gene are a known mechanism of disease (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 30530636, 31776437, 22962301, 10712197, 2121369, 25486365)
Juno Genomics, Hangzhou Juno Genomics, Inc RCV002497070 SCV005415708 likely pathogenic Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis criteria provided, single submitter clinical testing PM2_Supporting+PS4_Moderate+PP4+PVS1_Moderate

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