ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.1393-1555C>G

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV003165059 SCV003854955 likely pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2022-11-09 criteria provided, single submitter clinical testing The c.1393-1555C>G intronic variant results from a C to G substitution 1555 nucleotides upstream from coding exon 13 in the NF1 gene. This nucleotide position is highly conserved in available vertebrate species. This variant (reported as 1393-1554C>G) has been detected in an individual with a clinical diagnosis of neurofibromatosis type 1 (Giugliano T et al. Genes (Basel), 2019 07;10). In silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing (Giugliano T et al. Genes (Basel), 2019 07;10; Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Invitae RCV003778941 SCV004642061 uncertain significance Neurofibromatosis, type 1 2023-12-08 criteria provided, single submitter clinical testing This sequence change falls in intron 12 of the NF1 gene. It does not directly change the encoded amino acid sequence of the NF1 protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with clinical features of neurofibromatosis-Noonan syndrome (PMID: 31370276). This variant is also known as c.1393-1554C>G. ClinVar contains an entry for this variant (Variation ID: 2447120). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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