Submissions for variant NM_005902.4(SMAD3):c.309A>G (p.Leu103=)

gnomAD frequency: 0.87365  dbSNP: rs1065080

Total submissions: 20

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000128169	SCV000171761	benign	not specified	2012-11-02	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000128169	SCV000269835	benign	not specified	2013-04-04	criteria provided, single submitter	clinical testing	Leu103Leu in exon 2 of SMAD3: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 12.7% (560/4402) of African American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs1065080).
PreventionGenetics, part of Exact Sciences	RCV000128169	SCV000311291	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000247318	SCV000317696	benign	Familial thoracic aortic aneurysm and aortic dissection	2014-11-19	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.
Eurofins Ntd Llc (ga)	RCV000128169	SCV000332954	benign	not specified	2015-07-17	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000247318	SCV000393479	benign	Familial thoracic aortic aneurysm and aortic dissection	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000989348	SCV000393480	benign	Aneurysm-osteoarthritis syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000989348	SCV000605214	benign	Aneurysm-osteoarthritis syndrome	2023-11-30	criteria provided, single submitter	clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000128169	SCV000740518	benign	not specified	2015-11-30	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000247318	SCV000910495	benign	Familial thoracic aortic aneurysm and aortic dissection	2018-03-16	criteria provided, single submitter	clinical testing
Mendelics	RCV000989348	SCV001139639	benign	Aneurysm-osteoarthritis syndrome	2019-05-28	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000128169	SCV001362471	benign	not specified	2019-08-09	criteria provided, single submitter	clinical testing
Invitae	RCV000247318	SCV001729738	benign	Familial thoracic aortic aneurysm and aortic dissection	2024-02-01	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000247318	SCV002043353	benign	Familial thoracic aortic aneurysm and aortic dissection	2019-05-09	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000989348	SCV002057751	benign	Aneurysm-osteoarthritis syndrome	2021-07-15	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000989348	SCV004815332	benign	Aneurysm-osteoarthritis syndrome	2024-02-05	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000128169	SCV001744230	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000128169	SCV001808646	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000128169	SCV001967036	benign	not specified		no assertion criteria provided	clinical testing
Cohesion Phenomics	RCV003148654	SCV003836801	benign	Thoracic aortic aneurysm	2022-09-23	no assertion criteria provided	clinical testing