ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.1185G>A (p.Lys395=) (rs1567835847)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000705299 SCV000834289 likely pathogenic Neurofibromatosis, type 1 2019-02-20 criteria provided, single submitter clinical testing This sequence change affects codon 395 of the NF1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the NF1 protein. This variant also falls at the last nucleotide of exon 10 of the NF1 coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals with clinically diagnosed or suspected neurofibromatosis type 1 (NF1) (PMID: 24789688, 22034633, Invitae). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this silent change leads to skipping of exon 8 (PMID: 24789688). 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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