ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.1527+1G>C

dbSNP: rs1060500331
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000497180 SCV001233331 pathogenic Neurofibromatosis, type 1 2023-08-11 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 431589). Disruption of this splice site has been observed in individuals with neurofibromatosis type 1 (PMID: 10451518, 15060124). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 13 of the NF1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site 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).
Genetics and Molecular Pathology, SA Pathology RCV000497180 SCV002761433 likely pathogenic Neurofibromatosis, type 1 2021-12-02 criteria provided, single submitter clinical testing
Medical Genetics, University of Parma RCV000497180 SCV000588725 likely pathogenic Neurofibromatosis, type 1 2017-02-02 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004551621 SCV004726317 pathogenic NF1-related disorder 2023-11-30 no assertion criteria provided clinical testing The NF1 c.1527+1G>C variant is predicted to disrupt the GT donor site and interfere with normal splicing. This variant has been reported in an individual with neurofibromatosis type 1 (see for example - Mattocks et al. 2004. PubMed ID: 15060124). This variant has not been reported in a large population database, indicating this variant is rare. Variants that disrupt the consensus splice donor site in NF1 are expected to be pathogenic and alternate nucleotide substitutions affecting this nucleotide (c.1527+1G>A, c.1527+1G>T) have been reported as pathogenic (Pros et al. 2008. PubMed ID: 18546366). This variant is interpreted as pathogenic.

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