ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.1260+2T>C

dbSNP: rs1555611110
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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 RCV001037303 SCV001200712 pathogenic Neurofibromatosis, type 1 2024-08-01 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 11 of the NF1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or altered protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with clinical features of neurofibromatosis type 1 (PMID: 10677298; Invitae). ClinVar contains an entry for this variant (Variation ID: 836228). Studies have shown that disruption of this splice site results in inclusion of 13 base pairs of intronic sequence, and produces a non-functional protein and/or introduces a premature termination codon (PMID: 10677298). For these reasons, this variant has been classified as Pathogenic.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001037303 SCV001479143 pathogenic Neurofibromatosis, type 1 2020-10-26 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001037303 SCV002561648 likely pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV004559844 SCV005047285 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2024-02-20 criteria provided, single submitter clinical testing The c.1260+2T>C intronic pathogenic mutation results from a T to C substitution two nucleotides after coding exon 11 in the NF1 gene. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This variant has been observed in multiple individuals with a personal and/or family history that is consistent with Neurofibromatosis type 1 (Ambry internal data). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation.

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