Submissions for variant NM_001042492.3(NF1):c.2326-1G>C

dbSNP: rs1567848100

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000704705	SCV000833664	pathogenic	Neurofibromatosis, type 1	2020-09-23	criteria provided, single submitter	clinical testing	This sequence change affects an acceptor splice site in intron 19 of the NF1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Disruption of this splice site has been observed in individual(s) with neurofibromatosis type 1 (PMID: 12552569, 27838393). ClinVar contains an entry for this variant (Variation ID: 581003). This variant is not present in population databases (ExAC no frequency).
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV000704705	SCV001479170	likely pathogenic	Neurofibromatosis, type 1	2020-10-26	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000704705	SCV002561749	likely pathogenic	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing