Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000519310 | SCV000621334 | uncertain significance | not provided | 2017-10-03 | criteria provided, single submitter | clinical testing | The N1149S variant in the FBN1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The N1149S variant is observed in 1/15,304 (0.007%) alleles from individuals of African background and in 6/111,710 (0.005%) alleles from individuals of non-Finnish European background in the gnomAD dataset (Lek et al., 2016). The N1149S variant is a conservative amino acid substitution, which occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret N1149S as a variant of uncertain significance. |
Color Diagnostics, |
RCV001180375 | SCV001345295 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-02-03 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with serine at codon 1149 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 9/251474 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. |
Invitae | RCV001858030 | SCV002284166 | benign | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2022-12-06 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002490922 | SCV002781788 | 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 | 2021-08-03 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV004003641 | SCV004814806 | uncertain significance | Marfan syndrome | 2023-11-30 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with serine at codon 1149 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 9/251474 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. |