ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.986T>C (p.Ile329Thr)

gnomAD frequency: 0.00737  dbSNP: rs12324002
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Total submissions: 22
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen FBN1 Variant Curation Expert Panel, ClinGen RCV000029796 SCV004037327 benign Marfan syndrome 2023-09-26 reviewed by expert panel curation NM_000138.5 c.986T>C is a missense variant in FBN1 predicted to cause a substitution of an isoleucine by a threonine at amino acid 329 (p.Ile329Thr). This variant has been identified in numerous individuals with diagnoses or suspicion of Marfan syndrome in both the published literature and internal databases (PP4; PMIDs: 19293843, 24793577; Bichat, Mayo, UZG, UZA); however, in at least 2 of these cases, another pathogenic variant in FBN1 was also present (BP2; Bichat). This variant has been previously reported in ClinVar as likely benign or benign by more than 15 laboratories (Variation ID: 36133). It is present in gnomAD v3.1.2 at a frequency of 2.36% (977/41430 alleles) in the African/African American sub-population and is in the homozygous state in 17 total individuals (BA1; https://gnomad.broadinstitute.org/). Computational prediction tools and conservation analysis is unclear about a predicted impact of this variant. In summary, this variant meets criteria to be classified as benign for Marfan syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen FBN1 VCEP: BA1, BP2, PP4. The pathogenic evidence code PP4 was not considered to be in conflict with this conclusion.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000035295 SCV000058943 benign not specified 2014-09-22 criteria provided, single submitter clinical testing Ile329Thr in exon 9 of FBN1: This variant is not expected to have clinical signi ficance because it has been identified in 2.3% (103/4394) of African American ch romosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EV S/; dbSNP rs12324002).
GeneDx RCV001711086 SCV000168430 benign not provided 2018-12-17 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 24793577, 19293843, 27153395, 26332594)
Eurofins Ntd Llc (ga) RCV000035295 SCV000232911 benign not specified 2014-12-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000248877 SCV000317373 benign Familial thoracic aortic aneurysm and aortic dissection 2015-07-20 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Illumina Laboratory Services, Illumina RCV000248877 SCV000392634 likely benign Familial thoracic aortic aneurysm and aortic dissection 2018-02-02 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina RCV000029796 SCV000392635 likely benign Marfan syndrome 2018-02-02 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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina RCV000318940 SCV000392636 likely benign Geleophysic dysplasia 2018-02-02 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina RCV000357359 SCV000392637 likely benign Acromicric dysplasia 2018-02-02 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina RCV000260104 SCV000392638 likely benign Stiff skin syndrome 2018-02-02 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina RCV000317702 SCV000392639 likely benign Ectopia lentis 1, isolated, autosomal dominant 2018-02-02 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina RCV000286405 SCV000392641 likely benign Weill-Marchesani syndrome 2018-02-02 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Invitae RCV000757263 SCV000557039 benign Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2024-01-28 criteria provided, single submitter clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000029796 SCV000781326 uncertain significance Marfan syndrome 2016-11-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001711086 SCV000885415 benign not provided 2023-04-21 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000248877 SCV000901060 benign Familial thoracic aortic aneurysm and aortic dissection 2016-08-02 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000248877 SCV000903192 benign Familial thoracic aortic aneurysm and aortic dissection 2018-03-09 criteria provided, single submitter clinical testing
Mendelics RCV000029796 SCV001139623 benign Marfan syndrome 2019-05-28 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002276588 SCV002566551 likely benign Connective tissue disorder 2019-08-01 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000029796 SCV004823094 benign Marfan syndrome 2024-02-05 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000029796 SCV000052451 benign Marfan syndrome 2012-01-27 no assertion criteria provided clinical testing
Center for Medical Genetics Ghent, University of Ghent RCV000029796 SCV000787434 likely benign Marfan syndrome 2017-11-07 no assertion criteria provided clinical testing

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