Submissions for variant NM_001042492.3(NF1):c.7153AACTTT[1] (p.2385NF[1])

dbSNP: rs864622639

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000206539	SCV000261489	pathogenic	Neurofibromatosis, type 1	2025-01-26	criteria provided, single submitter	clinical testing	This variant, c.7096_7101del, results in the deletion of 2 amino acid(s) of the NF1 protein (p.Asn2366_Phe2367del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with neurofibromatosis (PMID: 8081387, 10862084, 18546366, 24789688). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 220715). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV002315635	SCV000663092	pathogenic	Hereditary cancer-predisposing syndrome; Cardiovascular phenotype	2024-01-24	criteria provided, single submitter	clinical testing	The c.7096_7101delAACTTT (p.N2366_F2367del) alteration, located in coding exon 47 of the NF1 gene, results from an in-frame deletion of 6 nucleotides at positions c.7096 to c.7101. This results in the deletion of 2 amino acids between codons 2366 and 2367. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been reported in in several unrelated individuals with a clinical diagnoses of NF1 and was confirmed as a de novo mutation in one individual with sporadic NF1. This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis (Choi, 2012). Based on the available evidence, this alteration is classified as pathogenic.
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	pathogenic	not provided	2022-05-11	criteria provided, single submitter	clinical testing	In-frame deletion of 2 amino acids in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Also known as p.2366delNF; This variant is associated with the following publications: (PMID: 32405727, 25293717, 18546366, 12807981, 25541118, 10862084, 8081387, 30014477, 31766501, 31533797, 31776437, 33372952)
The Laboratory of Genetics and Metabolism, Hunan Children’s Hospital	RCV001009584	SCV001169685	pathogenic	Neurofibromatosis, type 1; Tibial pseudarthrosis	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 Center for Human Genetics Tuebingen	RCV000680827	SCV001249056	pathogenic	not provided	2019-12-01	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV000206539	SCV001479216	pathogenic	Neurofibromatosis, type 1	2020-10-26	criteria provided, single submitter	clinical testing
AiLife Diagnostics, AiLife Diagnostics	RCV000680827	SCV002503006	likely pathogenic	not provided	2020-05-28	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000206539	SCV002560558	likely pathogenic	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000680827	SCV002771573	pathogenic	not provided	2022-06-17	criteria provided, single submitter	clinical testing	This variant has been identified in multiple unrelated individuals with clinical features of NF1, including at least one apparent de novo case. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In some published literature, this variant is referred to as c.7159_7164del.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000206539	SCV003837582	pathogenic	Neurofibromatosis, type 1	2023-03-09	criteria provided, single submitter	clinical testing
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV000206539	SCV005417371	pathogenic	Neurofibromatosis, type 1		criteria provided, single submitter	clinical testing	PM2_Supporting+PM4+PS4+PM6_Supporting+PP1+PP4
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000680827	SCV005876165	pathogenic	not provided	2024-01-22	criteria provided, single submitter	clinical testing	The NF1 c.7159_7164del; p.Asn2387_Phe2388del variant (rs864622639), also known as 7096_7101del, is reported as a common recurrent pathogenic variant in several individuals with NF1 (Abernathy 1994, Ars 2003, Messian 2000, Riva 2022, Xu 2014). This variant is also reported in ClinVar (Variation ID: 220715). It is absent from the Genome Aggregation Database (v2.1.1), indicating it is not a common polymorphism. This variant deletes two amino acid residues leaving the rest of the protein in-frame. Based on available information, this variant is considered to be pathogenic. References: Abernathy CR et al. Two NF1 mutations: frameshift in the GAP-related domain, and loss of two codons toward the 3' end of the gene. Hum Mutat. 1994;3(4):347-52. PMID: 8081387. Ars E et al. Recurrent mutations in the NF1 gene are common among neurofibromatosis type 1 patients. J Med Genet. 2003 Jun;40(6):e82. PMID: 12807981. Messiaen LM et al. Exhaustive mutation analysis of the NF1 gene allows identification of 95% of mutations and reveals a high frequency of unusual splicing defects. Hum Mutat. 2000;15(6):541-55. PMID: 10862084. Riva M et al. Recurrent NF1 gene variants and their genotype/phenotype correlations in patients with Neurofibromatosis type I. Genes Chromosomes Cancer. 2022 Jan;61(1):10-21. PMID: 34427956. Xu W et al. Fifty-four novel mutations in the NF1 gene and integrated analyses of the mutations that modulate splicing. Int J Mol Med. 2014 Jul;34(1):53-60. PMID: 24789688.
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine	RCV001257534	SCV001434360	pathogenic	Rhabdomyosarcoma	2020-09-01	no assertion criteria provided	provider interpretation
PreventionGenetics, part of Exact Sciences	RCV004737331	SCV005360260	pathogenic	NF1-related disorder	2023-10-30	no assertion criteria provided	clinical testing	The NF1 c.7159_7164del6 variant is predicted to result in an in-frame deletion (p.Asn2387_Phe2388del). This variant is often reported as c.7096_7101del (p.Asn2366_Phe2367del) in the literature. This variant was reported in individuals with Neurofibromatosis 1 (see examples: Abernathy et al. 1994. PubMed ID: 8081387; Zhu et al. 2019. PubMed ID: 31533797; Riva et al. 2021. PubMed ID: 34427956; Courtney. 2020. PubMed ID: 32405727;  Ulusal et al. 2017. PubMed ID: 28924536). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. In ClinVar, this variant is interpreted as pathogenic (https://preview.ncbi.nlm.nih.gov/clinvar/variation/220715/). This variant is interpreted as pathogenic.