ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.3942G>A (p.Trp1314Ter)

dbSNP: rs2067194816
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001053735 SCV001218011 pathogenic Neurofibromatosis, type 1 2024-05-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp1314*) 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, 22190595, 23404336). ClinVar contains an entry for this variant (Variation ID: 849712). For these reasons, this variant has been classified as Pathogenic.
Sema4, Sema4 RCV002256665 SCV002527541 likely pathogenic Hereditary cancer-predisposing syndrome 2021-08-16 criteria provided, single submitter curation
Genome-Nilou Lab RCV001053735 SCV002560007 pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002374921 SCV002624402 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2019-10-14 criteria provided, single submitter clinical testing The p.W1314* pathogenic mutation (also known as c.3942G>A), located in coding exon 29 of the NF1 gene, results from a G to A substitution at nucleotide position 3942. This changes the amino acid from a tryptophan to a stop codon within coding exon 29. This mutation has been detected in multiple patients with a clinical diagnosis of Neurofibromatosis Type 1 (NF1) (Upadhyaya M et al. Hum. Genet., 1997 Jan;99:88-92; Violante IR et al. Brain, 2013 Mar;136:918-25). 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.
GeneDx RCV002464361 SCV002758945 pathogenic not provided 2022-06-08 criteria provided, single submitter clinical testing Nonsense 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: 25525159, 9003501, 10712197, 23913538, 33000474, MehtaA2019[abstract], 23404336, 31766501, 22190595)

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