Submissions for variant NM_001042492.3(NF1):c.1796G>A (p.Trp599Ter)

dbSNP: rs1131691130

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002311257	SCV000581358	pathogenic	Hereditary cancer-predisposing syndrome; Cardiovascular phenotype	2016-11-23	criteria provided, single submitter	clinical testing	The p.W599* pathogenic mutation (also known as c.1796G>A), located in coding exon 16 of the NF1 gene, results from a G to A substitution at nucleotide position 1796. This changes the amino acid from a tryptophan to a stop codon within coding exon 16. This pathogenic mutation was identified in a patient with sporadic neurofibromatosis type 1 (NF1) who met clinical criteria (Ars E et al. Hum. Mol. Genet., 2000 Jan;9:237-47). 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001217607	SCV001389453	pathogenic	Neurofibromatosis, type 1	2024-05-26	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Trp599*) 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: 10607834). ClinVar contains an entry for this variant (Variation ID: 429013). 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.
GeneDx	RCV001799669	SCV002044128	pathogenic	not provided	2024-03-28	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: 10607834, 24676424, 31155235)
Genome-Nilou Lab	RCV001217607	SCV002561709	pathogenic	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV001217607	SCV005417351	pathogenic	Neurofibromatosis, type 1		criteria provided, single submitter	clinical testing	PM2_Supporting+PVS1+PP4