Submissions for variant NM_001042492.3(NF1):c.3498C>T (p.Gly1166=)

gnomAD frequency: 0.00392  dbSNP: rs2066733

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000130838	SCV000185736	benign	Hereditary cancer-predisposing syndrome	2014-06-30	criteria provided, single submitter	clinical testing	General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Invitae	RCV000204550	SCV000262400	benign	Neurofibromatosis, type 1	2024-02-01	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000214487	SCV000269453	benign	not specified	2014-11-24	criteria provided, single submitter	clinical testing	Gly1166Gly in exon 27 of NF1: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 1.1% (49/4406) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2066733).
PreventionGenetics, part of Exact Sciences	RCV000214487	SCV000306259	benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000680334	SCV000519043	benign	not provided	2017-09-15	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000204550	SCV000781988	uncertain significance	Neurofibromatosis, type 1	2016-11-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000680334	SCV000884232	benign	not provided	2017-12-12	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000214487	SCV000919871	benign	not specified	2017-10-23	criteria provided, single submitter	clinical testing	Variant summary: The NF1 c.3498C>T (p.Gly1166Gly) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 335/277088 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.012777 (307/24028). This frequency is about 61 times the estimated maximal expected allele frequency of a pathogenic NF1 variant (0.0002084), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likley benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV000204550	SCV001479294	benign	Neurofibromatosis, type 1	2020-10-26	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000214487	SCV002064919	benign	not specified	2019-06-06	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000130838	SCV002527516	benign	Hereditary cancer-predisposing syndrome	2021-06-02	criteria provided, single submitter	curation
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003315898	SCV004016449	benign	Neurofibromatosis, familial spinal	2023-07-07	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000680334	SCV004222166	likely benign	not provided	2014-05-07	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000214487	SCV001809430	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000214487	SCV001966551	benign	not specified		no assertion criteria provided	clinical testing