ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.1527+1G>A (rs1060500331)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000599578 SCV000709952 likely pathogenic not provided 2018-01-29 criteria provided, single submitter clinical testing The c.1527+1 G>A splice site variant has been previously reported as IVS10b+1 G>A using alternate nomenclature in association with neurofibromatosis type 1 (Ars et al., 1999). This variant destroys the canonical splice donor site in intron 13, and leads to the in-frame skipping of exon 13 (Ars et al., 1999). The variant is not observed in large population cohorts (Lek et al., 2016). In summary, we consider this variant to be likely pathogenic.
Invitae RCV000632460 SCV000753644 pathogenic Neurofibromatosis, type 1 2017-12-15 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 13 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 affected with neurofibromatosis type 1 (PMID: 10451518, 18546366) and in individuals in the Leiden Open-source Variation Database (PMID: 21520333). This variant is also know as IVS10b+1G>A in the literature. Experimental studies have shown that this splice site variant results in exon 13 skipping  (PMID: 10451518, 18546366). 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). For these reasons, this variant has been classified as Pathogenic.

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