Submissions for variant NM_001042492.3(NF1):c.6033A>G (p.Leu2011=)

gnomAD frequency: 0.00006  dbSNP: rs147995863

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000166155	SCV000216928	likely benign	Hereditary cancer-predisposing syndrome	2014-10-17	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx	RCV000436834	SCV000532071	likely benign	not provided	2021-06-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001086357	SCV000554910	likely benign	Neurofibromatosis, type 1	2025-02-03	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001086357	SCV001284314	likely benign	Neurofibromatosis, type 1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001125268	SCV001284315	likely benign	Neurofibromatosis, familial spinal	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001125269	SCV001284316	likely benign	Café-au-lait macules with pulmonary stenosis	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001125270	SCV001284317	benign	Neurofibromatosis-Noonan syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
CeGaT Center for Human Genetics Tuebingen	RCV000436834	SCV001500118	likely benign	not provided	2023-01-01	criteria provided, single submitter	clinical testing	NF1: BP4, BP7
Genetic Services Laboratory, University of Chicago	RCV001818389	SCV002064751	likely benign	not specified	2020-09-23	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000166155	SCV002527636	likely benign	Hereditary cancer-predisposing syndrome	2021-01-18	criteria provided, single submitter	curation
Genome-Nilou Lab	RCV001086357	SCV002560865	benign	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004552917	SCV004766227	likely benign	NF1-related disorder	2022-03-10	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).