ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.6579+1G>A (rs1060500345)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000626639 SCV000747341 pathogenic Cafe-au-lait spot 2017-01-01 criteria provided, single submitter clinical testing
GeneDx RCV000680831 SCV000808279 pathogenic not provided 2017-07-19 criteria provided, single submitter clinical testing This variant is denoted NF1 c.6579+1G>A or IVS42+1G>A and consists of a G>A nucleotide substitution at the +1 position of intron 42 of the NF1 gene. This variant destroys a canonical splice donor site and is predicted to cause abnormal gene splicing, leading to either an abnormal message that is subject to nonsense-mediated mRNA decay or to an abnormal protein product. This variant has been reported in at least one individual undergoing NF1 testing for a suspicion of neurofibromatosis type 1 (Lee 2006). Based on the current evidence, we consider this variant to be pathogenic.
Invitae RCV000703911 SCV000832837 likely pathogenic Neurofibromatosis, type 1 2018-03-20 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 42 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 reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333), and in an individual affected with neurofibromatosis type 1 (PMID: 16835897). 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). 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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