Submissions for variant NM_000138.5(FBN1):c.6997+17C>G

gnomAD frequency: 0.67656  dbSNP: rs363832

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000125022	SCV000168462	benign	not specified	2012-11-02	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.
PreventionGenetics, part of Exact Sciences	RCV000125022	SCV000302585	benign	not specified		criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001812034	SCV000603615	benign	not provided	2023-11-30	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000125022	SCV000917340	benign	not specified	2018-02-14	criteria provided, single submitter	clinical testing	Variant summary: FBN1 c.6997+17C>G alters a non-conserved nucleotide located 17 nucleotides away from a canonical splice site. The variant allele was found at a frequency of 0.74 in 276312 control chromosomes, suggesting that it is the major allele and therefore benign. The observed variant frequency is approximately 6567 fold above the estimated maximal expected allele frequency for a pathogenic variant in FBN1 causing Marfan Syndrome phenotype (0.00011), strongly suggesting that the variant is benign. The c.6997+17C>G variant has been reported in the literature and these reports classify the variant as a benign polymorphism. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002055535	SCV002409811	benign	Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection	2024-02-01	criteria provided, single submitter	clinical testing
Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	RCV000125022	SCV004233938	benign	not specified	2024-01-24	criteria provided, single submitter	clinical testing	This variant is classified as Benign based on local population frequency. This variant was detected in 95% of patients studied by a panel of primary immunodeficiencies. Number of patients: 84. Only high quality variants are reported.
Breakthrough Genomics, Breakthrough Genomics	RCV001812034	SCV005292937	benign	not provided		criteria provided, single submitter	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000125022	SCV001744256	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000125022	SCV001809481	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000125022	SCV001971259	benign	not specified		no assertion criteria provided	clinical testing
Cohesion Phenomics	RCV003148652	SCV003836751	benign	Marfan syndrome	2022-09-23	no assertion criteria provided	clinical testing