Submissions for variant NM_001042492.3(NF1):c.3525_3526del (p.Arg1176fs)

dbSNP: rs1131691092

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000492575	SCV000581287	pathogenic	Hereditary cancer-predisposing syndrome	2015-08-20	criteria provided, single submitter	clinical testing	Thec.3525_3526delAApathogenic mutation, located in codingexon27 of theNF1gene, results from a deletion of two nucleotides at nucleotide positions 3525 and 3526, causing a translationalframeshiftwith a predicted alternate stopcodon. This mutation has been detected in multiple individuals who meet NIH clinical criteria for NF1(FahsoldR, et al. Am. J. Hum. Genet. 2000;66(3):790-818;Trovó-MarquiAB, et al.Braz. J. Med.Biol. Res. 2005;38(9):1441-7;BrinckmannA, et al. Electrophoresis 2007;28(23):4295-301).In addition to the clinical data presented in the literature, sinceframeshiftsare typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMGRecommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
GeneDx	RCV000599249	SCV000709954	pathogenic	not provided	2022-12-22	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 3525delAA; This variant is associated with the following publications: (PMID: 18546366, 21031597, 18041031, 22155606, 31776437, 26969325, 16941471, 16138229, 30308447, 10712197)
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000660037	SCV000781989	pathogenic	Neurofibromatosis, type 1	2016-11-01	criteria provided, single submitter	clinical testing
Invitae	RCV000660037	SCV000812996	pathogenic	Neurofibromatosis, type 1	2022-09-30	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg1176Serfs*18) 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 premature translational stop signal has been observed in individuals with neurofibromatosis type 1 (PMID: 10712197, 17914445, 18546366, 22155606, 26969325). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 428971). This variant is also known as c.3525delAA.
CeGaT Center for Human Genetics Tuebingen	RCV000599249	SCV001247194	pathogenic	not provided	2017-08-01	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV000660037	SCV001479136	pathogenic	Neurofibromatosis, type 1	2020-10-26	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV000599249	SCV001832385	pathogenic	not provided	2019-11-30	criteria provided, single submitter	clinical testing
3billion	RCV000660037	SCV002521255	pathogenic	Neurofibromatosis, type 1	2022-05-22	criteria provided, single submitter	clinical testing	The variant is not observed in the gnomAD v2.1.1 dataset. Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000428971 / PMID: 10712197). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Genome-Nilou Lab	RCV000660037	SCV002559968	pathogenic	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000660037	SCV002576407	pathogenic	Neurofibromatosis, type 1	2022-08-04	criteria provided, single submitter	clinical testing	_x000D_ Criteria applied: PVS1, PS4_MOD, PM2_SUP