Submissions for variant NM_001042492.3(NF1):c.2189dup (p.Asn730fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003496032	SCV004324954	pathogenic	Neurofibromatosis, type 1	2023-09-22	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Asn730Lysfs*7) 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. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV004558163	SCV005047531	pathogenic	Hereditary cancer-predisposing syndrome; Cardiovascular phenotype	2023-05-22	criteria provided, single submitter	clinical testing	The c.2189dupA pathogenic mutation, located in coding exon 18 of the NF1 gene, results from a duplication of A at nucleotide position 2189, causing a translational frameshift with a predicted alternate stop codon (p.N730Kfs*7). 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.