Submissions for variant NM_001042492.3(NF1):c.1786del (p.Ile596fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV004997820	SCV005624526	likely pathogenic	not provided	2024-07-09	criteria provided, single submitter	clinical testing	The NF1 c.1786del (p.Ile596Phefs*9) variant alters the translational reading frame of the NF1 mRNA and is predicted to cause the premature termination of NF1 protein synthesis. This variant has not been reported in individuals with NF1-related conditions in the published literature. This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV005112499	SCV005763952	pathogenic	Neurofibromatosis, type 1	2024-08-12	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ile596Phefs*9) 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 variant has not been reported in the literature in individuals affected with NF1-related conditions. 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.