Submissions for variant NM_001042492.3(NF1):c.3822_3823del (p.Phe1275fs)

dbSNP: rs1555615472

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000546341	SCV000628548	pathogenic	Neurofibromatosis, type 1	2023-07-18	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 457670). This variant is also known as 3818delCT. 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.Phe1275Profs*8) 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).
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000546341	SCV000781999	pathogenic	Neurofibromatosis, type 1	2016-11-01	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV000546341	SCV001479229	pathogenic	Neurofibromatosis, type 1	2020-10-26	criteria provided, single submitter	clinical testing
GeneDx	RCV001545489	SCV001764831	pathogenic	not provided	2020-10-29	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 in large population cohorts (Lek 2016); This variant is associated with the following publications: (PMID: 18546366, 10607834, 16944272, 10712197)
Athena Diagnostics	RCV001545489	SCV001879393	pathogenic	not provided	2021-04-01	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant has been identified in multiple unrelated individuals with clinical features associated with this gene. In some published literature, this variant is referred to as c.3818delCT.
Genome-Nilou Lab	RCV000546341	SCV002559991	pathogenic	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004553184	SCV004116470	pathogenic	NF1-related disorder	2022-10-18	criteria provided, single submitter	clinical testing	The NF1 c.3822_3823delCT variant is predicted to result in a frameshift and premature protein termination (p.Phe1275Profs*8). This variant has been reported in multiple individuals with neurofibromatosis type 1 (Table 1 - 3818delCT - Ars et al. 2000. PubMed ID: 10607834; Table 4 - 3822delCT - Fahsold et al. 2000. PubMed ID: 10712197; Table 1 - Griffiths et al. 2007. PubMed ID: 16944272; Table S1 - Pros et al. 2008. PubMed ID: 18546366) and has been interpreted as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/457670/). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Frameshift variants in NF1 are expected to be pathogenic. This variant is interpreted as pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001545489	SCV004222167	pathogenic	not provided	2021-04-01	criteria provided, single submitter	clinical testing	The NF1 c.3822_3823del (p.Phe1275Profs*8) variant alters the translational reading frame of the NF1 mRNA and causes the premature termination of NF1 protein synthesis. This variant has been reported in the published literature in individuals with neurofibromatosis 1 (NF1) (PMIDs: 31776437 (2020), 30014477 (2018), 18546366 (2008), 16944272 (2007), 10712197 (2000), 10607834 (2000)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as pathogenic.