ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.4669dup (p.Thr1557fs)

dbSNP: rs1555619033
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000599245 SCV000710063 pathogenic not provided 2017-11-14 criteria provided, single submitter clinical testing The c.4606dupA variant in the NF1 gene has been reported previously in association with NF1 (Bianchessi et al., 2015). The duplication causes a frameshift starting with codon Threonine 1536, changes this amino acid to an Asparagine residue and creates a premature Stop codon at position 7 of the new reading frame, denoted p.Thr1536AsnfsX7. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant is not observed in large population cohorts (Lek et al., 2016). In summary, we consider this variant to be pathogenic.
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000660062 SCV000782030 likely pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV002319048 SCV001184546 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2018-01-03 criteria provided, single submitter clinical testing The c.4606dupA pathogenic mutation, located in coding exon 34 of the NF1 gene, results from a duplication of A at nucleotide position 4606, causing a translational frameshift with a predicted alternate stop codon (p.T1536Nfs*7). This mutation has been reported in an Italian patient with a clinical diagnosis of neurofibromatosis type 1 (Bianchessi D et al. Mol Genet Genomic Med 2015 Nov;3(6):513-25). 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000660062 SCV001224846 pathogenic Neurofibromatosis, type 1 2023-08-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr1536Asnfs*7) 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: 26740943). ClinVar contains an entry for this variant (Variation ID: 503769). For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV000660062 SCV002560073 pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing

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