ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.5073AAG[1] (p.Arg1692del)

dbSNP: rs1555396789
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV000624129 SCV000740508 likely pathogenic not provided 2017-07-03 criteria provided, single submitter clinical testing
Invitae RCV000822861 SCV000963683 pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2023-11-01 criteria provided, single submitter clinical testing This variant, c.5076_5078del, results in the deletion of 1 amino acid(s) of the FBN1 protein (p.Arg1692del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with Marfan syndrome (PMID: 17657824, 27146836, 32679894; Invitae). ClinVar contains an entry for this variant (Variation ID: 520496). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000624129 SCV001758872 likely pathogenic not provided 2022-12-19 criteria provided, single submitter clinical testing Not observed in large population cohorts (gnomAD); In-frame deletion of one arginine amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 17657824, 34008892, 32679894, 27146836, 33844962)
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV000663762 SCV001976658 likely pathogenic Marfan syndrome 2021-10-01 criteria provided, single submitter clinical testing PM1, PM2, PM4, PP3
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001798930 SCV002041996 likely pathogenic Familial thoracic aortic aneurysm and aortic dissection 2021-07-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV001798930 SCV002642900 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2019-08-30 criteria provided, single submitter clinical testing The c.5076_5078delAAG variant (also known as p.R1692del) is located in coding exon 41 of the FBN1 gene. This variant results from an in-frame AAG deletion at nucleotide positions 5076 to 5078. This results in the in-frame deletion of an arginine at codon 1692, and is located in the TGFB#05 domain. This variant (also described as c.5074_5076delAGA) was first reported in a child with ectopia lentis and no other clinical findings of Marfan syndrome (MFS) at the time of evaluation (Comeglio P et al. Hum. Mutat., 2007 Sep;28:928). This variant has also been detected in an individual meeting clinical diagnostic criteria for MFS, as well as in his asymptomatic father (Poninska JK et al. J Transl Med, 2016 05;14:115). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Center for Medical Genetics Ghent, University of Ghent RCV000663762 SCV000787110 uncertain significance Marfan syndrome 2017-11-07 no assertion criteria provided clinical testing

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