ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.4076del (p.Pro1359fs)

dbSNP: rs1135402852
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000497034 SCV000782007 pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV000497034 SCV001234332 pathogenic Neurofibromatosis, type 1 2023-07-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Pro1359Leufs*26) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with neurofibromatosis type 1 (PMID: 9003501). ClinVar contains an entry for this variant (Variation ID: 431632). For these reasons, this variant has been classified as Pathogenic.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV000497034 SCV001479154 pathogenic Neurofibromatosis, type 1 2020-10-26 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001543563 SCV001762224 pathogenic not provided 2021-06-17 criteria provided, single submitter clinical testing
3billion RCV000497034 SCV002318530 pathogenic Neurofibromatosis, type 1 2022-03-22 criteria provided, single submitter clinical testing Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000431632, PMID:9003501). It is not observed in the gnomAD v2.1.1 dataset. Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Genome-Nilou Lab RCV000497034 SCV002560018 pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002323860 SCV002626477 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2021-06-25 criteria provided, single submitter clinical testing The c.4076delC pathogenic mutation, located in coding exon 30 of the NF1 gene, results from a deletion of one nucleotide at nucleotide position 4076, causing a translational frameshift with a predicted alternate stop codon (p.P1359Lfs*26). This alteration has been identified in at least two unrelated individuals with neurofibromatosis type 1 (Upadhyaya M et al. Hum Genet. 1997 Jan;99:88-92). 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.
Medical Genetics, University of Parma RCV000497034 SCV000588772 pathogenic Neurofibromatosis, type 1 2017-02-02 no assertion criteria provided clinical testing

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