ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.3113+2T>C

dbSNP: rs876658997
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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 RCV000497068 SCV001398642 pathogenic Neurofibromatosis, type 1 2023-10-13 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 23 of the NF1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with clinical features of neurofibromatosis type 1 (PMID: 18546366, 26056819; Invitae). ClinVar contains an entry for this variant (Variation ID: 431619). Studies have shown that disruption of this splice site results in skipping of exon 23, but is expected to preserve the integrity of the reading-frame (PMID: 18546366, 26056819). This variant disrupts the p.Met1035 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 31370276; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
MGZ Medical Genetics Center RCV000497068 SCV002581624 uncertain significance Neurofibromatosis, type 1 2022-07-28 criteria provided, single submitter clinical testing
Athena Diagnostics RCV002506199 SCV002817325 pathogenic not provided 2021-03-10 criteria provided, single submitter clinical testing This variant is expected to severely impact normal RNA splicing, and consequently, protein structure and/or function. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene (PMID: 18546366, 26056819).This observation is not an independent occurrence and has been identified in the same individual by RCIGM, the other laboratory participating in the GEMINI study.
Medical Genetics, University of Parma RCV000497068 SCV000588758 uncertain significance Neurofibromatosis, type 1 2017-02-02 no assertion criteria provided clinical testing

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