Submissions for variant NM_001042492.3(NF1):c.5235G>A (p.Lys1745=)

gnomAD frequency: 0.00305  dbSNP: rs17887014

Total submissions: 25

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163276	SCV000213804	benign	Hereditary cancer-predisposing syndrome	2014-06-19	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
Invitae	RCV000989812	SCV000261809	benign	Neurofibromatosis, type 1	2024-02-01	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000218424	SCV000269457	benign	not specified	2015-01-13	criteria provided, single submitter	clinical testing	p.Lys1745Lys in exon 37 of NF1: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 0.5% (42/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs17887014).
PreventionGenetics, part of Exact Sciences	RCV000218424	SCV000306275	benign	not specified		criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000436632	SCV000511467	likely benign	not provided	2016-06-15	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
GeneDx	RCV000436632	SCV000521064	benign	not provided	2017-07-18	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000436632	SCV000696398	benign	not provided	2016-08-31	criteria provided, single submitter	clinical testing	Variant summary: The NF1 c.5172G>A (p.Lys1724Lys) 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. 4/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE sites. This variant was found in 408/119678 control chromosomes (1 homozygote), predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.0047796 (314/65696). This frequency is about 23 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 European (Non-Finnish) origin. This variant has been reported in nF1 patients with classification of benign. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000436632	SCV000885833	benign	not provided	2023-10-16	criteria provided, single submitter	clinical testing
Mendelics	RCV000989812	SCV001140379	benign	Neurofibromatosis, type 1	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001128214	SCV001287627	likely benign	Neurofibromatosis-Noonan syndrome	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000989812	SCV001287628	likely benign	Neurofibromatosis, type 1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV001128215	SCV001287629	likely benign	Neurofibromatosis, familial spinal	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV001128216	SCV001287630	likely benign	Café-au-lait macules with pulmonary stenosis	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV000989812	SCV001479300	benign	Neurofibromatosis, type 1	2020-10-26	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000436632	SCV001747864	benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	NF1: BP4, BP7, BS1, BS2
Genetic Services Laboratory, University of Chicago	RCV000218424	SCV002071867	benign	not specified	2017-11-01	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000163276	SCV002527606	benign	Hereditary cancer-predisposing syndrome	2020-10-27	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000218424	SCV002550900	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000989812	SCV002560810	likely benign	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002336379	SCV002643691	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.
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV001128215	SCV004016405	benign	Neurofibromatosis, familial spinal	2023-07-07	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000436632	SCV001743426	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000218424	SCV001808817	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000218424	SCV001971666	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000436632	SCV002036354	likely benign	not provided		no assertion criteria provided	clinical testing