ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.2148A>G (p.Gly716=) (rs141039922)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000507578 SCV000603637 likely benign not specified 2016-10-05 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000727005 SCV000704864 uncertain significance not provided 2017-02-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV000620523 SCV000738788 likely benign Cardiovascular phenotype 2016-04-26 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign
Invitae RCV001089320 SCV000753161 benign Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2020-09-09 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000507578 SCV000917358 benign not specified 2018-07-02 criteria provided, single submitter clinical testing Variant summary: FBN1 c.2148A>G alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The observed variant frequency within African control individuals in the gnomAD database is approximately 12-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in FBN1 causing Marfan Syndrome phenotype (0.00011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. The variant, c.2148A>G, has been reported in the literature in individuals affected with Marfan Syndrome (Comeglio_2007). These report(s) do not provide unequivocal conclusions about association of the variant with Marfan Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "benign/likely benign" (3x) and "uncertain significance" (1x). Based on the evidence outlined above, the variant was classified as benign.
Color Health, Inc RCV001188645 SCV001355733 benign Familial thoracic aortic aneurysm and aortic dissection 2019-01-11 criteria provided, single submitter clinical testing

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