Submissions for variant NM_001042492.3(NF1):c.4882T>C (p.Leu1628=)

gnomAD frequency: 0.02270  dbSNP: rs10512435

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163175	SCV000213696	benign	Hereditary cancer-predisposing syndrome	2014-11-19	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
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000221784	SCV000269455	benign	not specified	2014-11-24	criteria provided, single submitter	clinical testing	Leu1628Leu in exon 37 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 7.0% (309/4406) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs10512435).
PreventionGenetics, part of Exact Sciences	RCV000221784	SCV000306272	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000372852	SCV000401757	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000278397	SCV000401758	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000352103	SCV000401759	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.
Illumina Laboratory Services, Illumina	RCV000388338	SCV000401760	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000589955	SCV000518974	benign	not provided	2016-04-05	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000278397	SCV000554870	benign	Neurofibromatosis, type 1	2025-02-04	criteria provided, single submitter	clinical testing
Medical Genetics, University of Parma	RCV000278397	SCV000588792	benign	Neurofibromatosis, type 1	2022-08-17	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000589955	SCV000604521	benign	not provided	2024-10-29	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589955	SCV000696395	benign	not provided	2016-05-11	criteria provided, single submitter	clinical testing	Variant summary: The NF1 c.4819T>C (p.Leu1607Leu) variant involves the alteration of a conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a benign outcome for this variant. This variant was found in 833/121372 control chromosomes (29 homozygotes) at a frequency of 0.0068632, which is approximately 33 times the estimated maximal expected allele frequency of a pathogenic NF1 variant (0.0002084), suggesting this variant is a benign polymorphism. Reputable database/clinical diagnostic laboratory cites this variant with classification of "Benign". Taken together, this variant is classified as Benign.
Athena Diagnostics	RCV000589955	SCV000842892	benign	not provided	2018-04-23	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV000278397	SCV001479296	benign	Neurofibromatosis, type 1	2020-10-26	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000278397	SCV002560780	benign	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002336378	SCV002637889	benign	Hereditary cancer-predisposing syndrome; Cardiovascular phenotype	2016-03-23	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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.
Breakthrough Genomics, Breakthrough Genomics	RCV000589955	SCV005253783	benign	not provided		criteria provided, single submitter	not provided
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000221784	SCV001807444	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000221784	SCV001966634	benign	not specified		no assertion criteria provided	clinical testing