Submissions for variant NM_001042492.3(NF1):c.2325+4T>C

dbSNP: rs1555613934

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000535397	SCV000628430	uncertain significance	Neurofibromatosis, type 1	2024-01-25	criteria provided, single submitter	clinical testing	This sequence change falls in intron 19 of the NF1 gene. It does not directly change the encoded amino acid sequence of the NF1 protein. It affects a nucleotide within the consensus splice site. 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. ClinVar contains an entry for this variant (Variation ID: 457578). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV002316496	SCV000666753	uncertain significance	Hereditary cancer-predisposing syndrome; Cardiovascular phenotype	2023-01-12	criteria provided, single submitter	clinical testing	The c.2325+4T>C intronic variant results from a T to C substitution 4 nucleotides after coding exon 19 in the NF1 gene. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing; however, direct evidence is insufficient at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab	RCV000535397	SCV002562025	uncertain significance	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002483370	SCV002789398	uncertain significance	Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis	2021-12-30	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004553183	SCV004714988	likely benign	NF1-related disorder	2021-03-19	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).