ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.7749del (p.Ile2584fs)

dbSNP: rs2151582195
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001979952 SCV002223919 pathogenic Neurofibromatosis, type 1 2020-12-10 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with clinical features of neurofibromatosis type 1 (PMID: 30828344). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ile2563Phefs*40) in the NF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538).
GeneDx RCV003120771 SCV003798628 pathogenic not provided 2022-08-08 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay 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: 30828344, 31370276)
Ambry Genetics RCV004558758 SCV005048813 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2023-06-08 criteria provided, single submitter clinical testing The c.7686delG pathogenic mutation, located in coding exon 52 of the NF1 gene, results from a deletion of one nucleotide at nucleotide position 7686, causing a translational frameshift with a predicted alternate stop codon (p.I2563Ffs*40). This alteration has been observed in multiple individuals with a personal and/or family history that is consistent with NF1-related disease (Micaglio E et al. Front Genet, 2019 Feb;10:50; Giugliano T et al. Genes (Basel), 2019 Jul;10; Napolitano F et al. Genes (Basel), 2022 Jun;13). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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