Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000181637 | SCV000233940 | uncertain significance | not provided | 2014-07-01 | criteria provided, single submitter | clinical testing | p.Lys2851Glu (AAA>GAA): c.8551 A>G in exon 66 of the FBN1 gene (NM_000138.4)A variant of unknown significance has been identified in the FBN1 gene. The K2851E variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The K2851E variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The K2851E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Furthermore, no missense mutations in nearby residues have been reported in association with Marfan syndrome, indicating that this region of the protein may be tolerant of change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in TAAD panel(s). |
Color Diagnostics, |
RCV001178820 | SCV001343354 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-10-19 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with glutamic acid at codon 2851 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). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with FBN1-related disorders in the literature. This variant has been identified in 2/251108 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 |
RCV001362745 | SCV001558778 | likely benign | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2023-11-27 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002485196 | SCV002786728 | uncertain significance | Ectopia lentis 1, isolated, autosomal dominant; Marfan syndrome; MASS syndrome; Stiff skin syndrome; Weill-Marchesani syndrome 2, dominant; Acromicric dysplasia; Geleophysic dysplasia 2; Progeroid and marfanoid aspect-lipodystrophy syndrome | 2022-03-15 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV003996701 | SCV004844881 | uncertain significance | Marfan syndrome | 2023-11-20 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with glutamic acid at codon 2851 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). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/251108 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. |