Submissions for variant NM_000267.3(NF1):c.4111delG

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003599134	SCV004491662	pathogenic	Neurofibromatosis, type 1	2022-12-03	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with NF1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val1371Trpfs*14) 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).
Ambry Genetics	RCV004992705	SCV005452053	pathogenic	Hereditary cancer-predisposing syndrome; Cardiovascular phenotype	2024-09-06	criteria provided, single submitter	clinical testing	The c.4111delG variant, located in coding exon 31 of the NF1 gene, results from a deletion of one nucleotide at nucleotide position 4111, causing a translational frameshift with a predicted alternate stop codon (p.V1371Wfs*14). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.