Submissions for variant NM_001042492.3(NF1):c.3497-1G>A

dbSNP: rs1555615004

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000560695	SCV000628526	likely pathogenic	Neurofibromatosis, type 1	2024-10-10	criteria provided, single submitter	clinical testing	This sequence change affects an acceptor splice site in intron 26 of the NF1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site 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). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with NF1-related conditions (PMID: 34418705). ClinVar contains an entry for this variant (Variation ID: 457652). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV000560695	SCV001479153	pathogenic	Neurofibromatosis, type 1	2020-10-26	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000560695	SCV002559964	likely pathogenic	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing