ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.3457_3460del (p.Leu1153fs) (rs1321848637)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165479 SCV000216210 pathogenic Hereditary cancer-predisposing syndrome 2014-08-20 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense);Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Invitae RCV000168453 SCV000219150 pathogenic Neurofibromatosis, type 1 2019-10-23 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu1153Metfs*4) in the NF1 gene. It is expected to result in an absent or disrupted protein product. This variant has been observed in several individuals affected with neurofibromatosis, type 1 (PMID: 9003501, 18546366, 21838856, 25541118, 26969325, 14517963). ClinVar contains an entry for this variant (Variation ID: 185963). Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). For these reasons, this variant has been classified as Pathogenic.
Medical Genetics, University of Parma RCV000168453 SCV000588761 pathogenic Neurofibromatosis, type 1 2019-12-20 criteria provided, single submitter clinical testing
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000168453 SCV000781986 pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000712406 SCV000842889 pathogenic not provided 2018-04-25 criteria provided, single submitter clinical testing
GeneDx RCV000712406 SCV001168586 pathogenic not provided 2019-08-23 criteria provided, single submitter clinical testing The c.3457_3460delCTCA variant has been reported previously in association with neurofibromatosis type 1 (Upadhyaya et al., 1997; Duat Rodriguez et al., 2015). The variant is not observed in large population cohorts (Lek et al., 2016). The deletion causes a frameshift starting with codon Leucine 1153, changes this amino acid to a Methionine residue and creates a premature Stop codon at position 4 of the new reading frame, denoted p.Leu1153MetfsX4. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. We interpret this variant as pathogenic.

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