ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.7458-17T>G

dbSNP: rs766585105
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Molecular Diagnostics, Institute of Oncology Ljubljana RCV000767383 SCV000840452 likely pathogenic Neurofibromatosis, type 1 2018-10-04 criteria provided, single submitter clinical testing The variant has been observed in a patient with Neurofibromatosis type I. The variants is predicted to create a de novo acceptor splice site in intron 50 by in silico splicing tools. Functional RNA study has shown that the variant causes major splicing aberration - retention of 16 intronic nucleotides, causing frameshift and introduction of premature stop codon at the amino acid residue 2465 (PMID: 31507634, 34439939). Therefore the variant was classified as likely pathogenic (ACMG/AMP: PS3, PM2, PP3, and PP1 supporting).
Labcorp Genetics (formerly Invitae), Labcorp RCV000767383 SCV003787096 likely pathogenic Neurofibromatosis, type 1 2021-12-12 criteria provided, single submitter clinical testing This sequence change falls in intron 49 of the NF1 gene. It does not directly change the encoded amino acid sequence of the NF1 protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with neurofibromatosis type 1 (PMID: 31507634). ClinVar contains an entry for this variant (Variation ID: 586981). Studies have shown that this variant is associated with altered splicing, but the impact on the resulting protein product is unknown (PMID: 31507634, 34439939). 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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