ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.5943+1G>A (rs1555534433)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000763392 SCV000894106 pathogenic Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000578724 SCV000680722 pathogenic not provided 2018-07-31 criteria provided, single submitter clinical testing The c.5943+1 G>A splice site variant has been previously reported in association with neurofibromatosis type 1 (Fahsold et al., 2000). This variant destroys the canonical splice donor site in intron 39, and is expected to cause abnormal gene splicing. The variant is not observed in large population cohorts (Lek et al., 2016). Other splice variants in the same donor site (c.5943+1 G>T, c.5943+2 T>G) have been reported in the Human Gene Mutation Database in association with neurofibromatosis type 1 (Stenson et al., 2014). In summary, we consider this variant to be pathogenic.
Invitae RCV000693088 SCV000820943 likely pathogenic Neurofibromatosis, type 1 2018-06-09 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 39 of the NF1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with neurofibromatosis type I (PMID: 10712197). ClinVar contains an entry for this variant (Variation ID: 488817). Donor and acceptor splice site variants 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). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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