ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.6601A>G (p.Met2201Val)

gnomAD frequency: 0.00001  dbSNP: rs776823384
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001525571 SCV001735731 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2020-07-20 criteria provided, single submitter clinical testing This missense variant replaces methionine with valine at codon 2201 of the FBN1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in one individual referred for aortopathy panel testing (PMID: 25944730) and one individual in the control cohort (PMID: 16220557). This variant has been identified in 7/251260 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV001525571 SCV002042009 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2019-11-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001869388 SCV002305884 uncertain significance Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2024-01-17 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2201 of the FBN1 protein (p.Met2201Val). This variant is present in population databases (rs776823384, gnomAD 0.01%). This missense change has been observed in individual(s) with FBN1-related conditions (PMID: 25944730, 33483584; Invitae). ClinVar contains an entry for this variant (Variation ID: 807242). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FBN1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV002481773 SCV002785471 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 2021-11-17 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004004430 SCV004822438 uncertain significance Marfan syndrome 2023-06-15 criteria provided, single submitter clinical testing This missense variant replaces methionine with valine at codon 2201 of the FBN1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in one individual referred for aortopathy panel testing (PMID: 25944730) and one individual in the control cohort (PMID: 16220557). This variant has been identified in 7/251260 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.

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.