Submissions for variant NM_000138.5(FBN1):c.2895G>A (p.Glu965=)

gnomAD frequency: 0.00038  dbSNP: rs140591

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035154	SCV000058795	likely benign	not specified	2012-10-23	criteria provided, single submitter	clinical testing	Glu965Glu in Exon 24 of FBN1: This variant is not expected to have clinical sign ificance because it does not alter the amino acid residue and it is not located within the splice consensus sequence. It has been identified in approximately 0. 1% (8/8592) of European American chromosomes from a broad population by the NHLB I Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs140591).
GeneDx	RCV000035154	SCV000168440	benign	not specified	2014-02-22	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000227421	SCV000283613	likely benign	Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection	2024-01-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000314502	SCV000392524	benign	Weill-Marchesani syndrome	2018-01-13	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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV000350683	SCV000392525	likely benign	Marfan syndrome	2018-01-13	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	RCV000406637	SCV000392526	benign	Acromicric dysplasia	2018-01-13	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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV000310979	SCV000392527	benign	Geleophysic dysplasia	2018-01-13	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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV000356235	SCV000392528	benign	Ectopia lentis 1, isolated, autosomal dominant	2018-01-13	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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV000297968	SCV000392530	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2018-01-13	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 Laboratory Services, Illumina	RCV000362108	SCV000392531	benign	Stiff skin syndrome	2018-01-13	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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000035154	SCV000603633	benign	not specified	2016-09-23	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000297968	SCV000738767	benign	Familial thoracic aortic aneurysm and aortic dissection	2017-01-09	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.
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000350683	SCV000807922	likely benign	Marfan syndrome	2018-06-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000297968	SCV000904502	benign	Familial thoracic aortic aneurysm and aortic dissection	2018-04-13	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001311041	SCV001501065	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	FBN1: BP4, BP7
All of Us Research Program, National Institutes of Health	RCV000350683	SCV004814858	benign	Marfan syndrome	2024-02-05	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001311041	SCV001809298	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001311041	SCV001967074	likely benign	not provided		no assertion criteria provided	clinical testing