ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.586+5del

dbSNP: rs1567820838
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000695136 SCV000823617 uncertain significance Neurofibromatosis, type 1 2018-02-13 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with NF1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 5 of the NF1 gene. It does not directly change the encoded amino acid sequence of the NF1 protein, but it affects a nucleotide within the consensus splice site of the intron. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. A different variant affecting the G nucleotide at intronic +5 (c.586+5G>A) has been determined to be likely pathogenic (PMID: 10607834, 18546366, 22617876, Invitae). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic.

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