Total submissions: 22
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
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, |
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). |
Gene |
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 |
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, |
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, |
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, |
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, |
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, |
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, |
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, |
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, |
RCV000029796 | SCV000781326 | uncertain significance | Marfan syndrome | 2016-11-01 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV001711086 | SCV000885415 | benign | not provided | 2023-04-21 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV000248877 | SCV000901060 | benign | Familial thoracic aortic aneurysm and aortic dissection | 2016-08-02 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
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, |
RCV002276588 | SCV002566551 | likely benign | Connective tissue disorder | 2019-08-01 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV000029796 | SCV004823094 | benign | Marfan syndrome | 2024-02-05 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000029796 | SCV000052451 | benign | Marfan syndrome | 2012-01-27 | no assertion criteria provided | clinical testing | |
Center for Medical Genetics Ghent, |
RCV000029796 | SCV000787434 | likely benign | Marfan syndrome | 2017-11-07 | no assertion criteria provided | clinical testing |