ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.7241G>A (p.Arg2414Gln) (rs143863014)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 12
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Center RCV000148488 SCV000267312 uncertain significance Marfan syndrome 2016-03-18 criteria provided, single submitter reference population
Invitae RCV000530970 SCV000627984 uncertain significance Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2017-05-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 2414 of the FBN1 protein (p.Arg2414Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs143863014, ExAC 0.009%). This variant has been reported in the literature in two individuals from the same family with suspected Marfan syndrome (PMID: 16835936). ClinVar contains an entry for this variant (Variation ID: 161234). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000995333 SCV001149445 uncertain significance not provided 2018-05-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001115601 SCV001273589 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001115602 SCV001273590 uncertain significance Acromicric dysplasia 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001115603 SCV001273591 uncertain significance Ectopia lentis, isolated, autosomal dominant 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV000148488 SCV001275175 uncertain significance Marfan syndrome 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001117026 SCV001275176 uncertain significance Stiff skin syndrome 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001117027 SCV001275177 uncertain significance Weill-Marchesani syndrome 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Color Health, Inc RCV001115601 SCV001349852 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2021-01-20 criteria provided, single submitter clinical testing This missense variant replaces arginine with glutamine at codon 2414 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 been reported in two related individuals with Marfan-related phenotype from a family with history of Marfan syndrome (PMID: 16835936). This variant has not been identified 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.
GeneDx RCV000995333 SCV001823126 uncertain significance not provided 2020-05-15 criteria provided, single submitter clinical testing Reported in individuals with suspected TAAD or Marfan syndrome who did not meet Ghent criteria (Sakai et al., 2006; Overwater et al., 2018); Identified in individuals referred for connective tissue disease genetic testing at GeneDx; however, one of these probands also harbored a second variant in FBN1 that likely contributed to the phenotype; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Although located in a calcium-binding EGF-like domain of the FBN1 gene, it does not affect a cysteine residue within this domain; cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with FBN1-related disorders (Collod-Beroud et al., 2003); Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 161234; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 29907982, 16835936, 25637381, 22913777, 27647783, 24941995, 25812041)
CSER _CC_NCGL, University of Washington RCV000148488 SCV000190192 likely benign Marfan syndrome 2014-06-01 no assertion criteria provided research

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.