ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.4720_4724del (p.Thr1574fs)

dbSNP: rs2067692232
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001269122 SCV001448370 likely pathogenic Neurofibromatosis, type 1 2020-11-30 criteria provided, single submitter clinical testing Variant summary: NF1 c.4657_4661delACTAG (p.Thr1553AlafsX5) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251142 control chromosomes. To our knowledge, no occurrence of c.4657_4661delACTAG in individuals affected with Neurofibromatosis Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001269122 SCV005749357 pathogenic Neurofibromatosis, type 1 2024-03-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr1553Alafs*5) 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 variant has not been reported in the literature in individuals affected with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 987799). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

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