ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.3941G>A (p.Trp1314Ter)

dbSNP: rs876658235
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000213654 SCV000273203 pathogenic Hereditary cancer-predisposing syndrome 2015-01-16 criteria provided, single submitter clinical testing The p.W1314* pathogenic mutation (also known as c.3941G>A), located in coding exon 29 of the NF1 gene, results from a G to A substitution at nucleotide position 3941. This changes the amino acid from a tryptophan to a stop codon within coding exon 29. A similar alteration leading to the same amino acid change, p.W1314* (c.3942G>A), has been identified in multiple patients meeting clinical NF1 criteria (Upadhyaya, M et al. Hum Genet. 1997 Jan;99(1):88-92; Violante, IR et al. Brain. 2013 Mar;136(Pt 3):918-25). In addition to the clinical data presented in the literature, since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Labcorp Genetics (formerly Invitae), Labcorp RCV003495119 SCV004297476 pathogenic Neurofibromatosis, type 1 2023-04-22 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 229852). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with neurofibromatosis, type 1 (PMID: 26740943). 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).
GeneDx RCV004719766 SCV005325959 pathogenic not provided 2023-04-25 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: 35641267, 31766501, 26740943)

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