ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.6704+1del

dbSNP: rs1597844692
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000806711 SCV000946725 pathogenic Neurofibromatosis, type 1 2023-04-27 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: 651367). Disruption of this splice site has been observed in individuals with neurofibromatosis type 1 (PMID: 15060124; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a splice site in intron 43 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).
CeGaT Center for Human Genetics Tuebingen RCV001092513 SCV001249054 likely pathogenic not provided 2019-10-01 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000806711 SCV002560204 pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
GeneDx RCV001092513 SCV003930885 pathogenic not provided 2023-06-12 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 15060124)
Ambry Genetics RCV004559681 SCV005048667 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2023-05-03 criteria provided, single submitter clinical testing The c.6641+1delG intronic pathogenic mutation, located in intron 43 of the NF1 gene, results from a deletion of one nucleotide within intron 43 of the NF1 gene. This alteration has been reported in an individual with a clinical diagnosis of neurofibromatosis type 1 (Mattocks C et al. J Med Genet, 2004 Apr;41:e48). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In silico splice site analysis predicts that this alteration will weaken the native splice donor site and will result in the creation or strengthening of a novel splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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