Submissions for variant NM_000267.3(NF1):c.7096_7101del (rs864622639)

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000206539	SCV000261489	pathogenic	Neurofibromatosis, type 1	2019-11-24	criteria provided, single submitter	clinical testing	This sequence change deletes 6 nucleotides from exon 47 of the NF1 mRNA (c.7096_7101delAACTTT). This leads to the deletion of 2 amino acid residues in the NF1 protein (p.Asn2366_Phe2367del) but otherwise preserves the integrity of the reading frame. This variant is described as a common recurrent pathogenic mutation in the NF1 gene and has been observed in families and many individuals affected with neurofibromatosis (PMID: 8081387, 10862084, 18546366, 24789688). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV000562847	SCV000663092	pathogenic	Hereditary cancer-predisposing syndrome	2017-12-27	criteria provided, single submitter	clinical testing	​The c.7096_7101delAACTTT pathogenic mutation (also known as p.N2366_F2367del) is located in coding exon 48 of the NF1 gene. This pathogenic mutation results from an in-frame AACTTT deletion between nucleotide positions 7096 and 7101. This results in an in-frame deletion of 2 amino acid residues at positions 2366 and 2367. This mutation has been reported as a common recurrent pathogenic mutation in several individuals with clinical diagnoses of NF1, and was confirmed as a de novo mutation in one individual with sporadic NF1 (Xu W et al. Int. J. Mol. Med., 2014 Jul;34:53-60; Pros E et al. Hum. Mutat. 2008 Sep;29(9):E173-93; Messiaen LM et al. Hum. Mutat. 2000;15(6):541-55; Abernathy CR et al. Hum. Mutat. 1994;3(4):347-52). Based on the available evidence, this variant is interpreted as a pathogenic mutation.
Center for Human Genetics, Inc,Center for Human Genetics, Inc	RCV000206539	SCV000782100	pathogenic	Neurofibromatosis, type 1	2016-11-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000680827	SCV000808275	likely pathogenic	not provided	2018-06-15	criteria provided, single submitter	clinical testing	The c.7096_7101delAACTTT variant has been published previously in association with neurofibromatosis type 1, including an apparently de novo occurrence (Abernathy et al., 1994; Messiaen et al., 2000; Duat et al., 2015). The variant is not observed in large population cohorts (Lek et al., 2016). It results in the in-frame deletion of 2 amino acids. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. In summary, this variant is likely pathogenic.
The Laboratory of Genetics and Metabolism, Hunan Children’s Hospital	RCV001009584	SCV001169685	pathogenic	Neurofibromatosis, type 1; Tibial pseudoarthrosis	2018-11-10	criteria provided, single submitter	research
Medical Genetics, University of Parma	RCV000206539	SCV001218929	pathogenic	Neurofibromatosis, type 1	2019-12-20	criteria provided, single submitter	clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000680827	SCV001249056	pathogenic	not provided	2019-12-01	criteria provided, single submitter	clinical testing
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine	RCV001257534	SCV001434360	pathogenic	Rhabdomyosarcoma (disease)	2020-09-01	no assertion criteria provided	provider interpretation