Submissions for variant NM_000138.5(FBN1):c.6055G>A (p.Glu2019Lys)

gnomAD frequency: 0.00004  dbSNP: rs377149130

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000761911	SCV000892131	likely benign	not provided	2018-08-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001178617	SCV001343108	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-06-07	criteria provided, single submitter	clinical testing	This missense variant replaces glutamic acid with lysine at codon 2019 of the FBN1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in two individuals who did not meet Marfan syndrome diagnosis but had a family history of Marfan syndrome (PMID: 21883168). This variant has been reported in an individual affected with sporadic sporadic abdominal aortic aneurysm (PMID 26017485). This variant has been identified in 6/281986 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002533889	SCV003466303	likely benign	Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection	2024-01-05	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003999912	SCV004814606	uncertain significance	Marfan syndrome	2023-11-30	criteria provided, single submitter	clinical testing	This missense variant replaces glutamic acid with lysine at codon 2019 of the FBN1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in two individuals who did not meet Marfan syndrome diagnosis but had a family history of Marfan syndrome (PMID: 21883168). This variant has been reported in an individual affected with sporadic sporadic abdominal aortic aneurysm (PMID 26017485). This variant has been identified in 6/281986 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000761911	SCV001809238	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000761911	SCV001965120	uncertain significance	not provided		no assertion criteria provided	clinical testing