Submissions for variant NM_004612.4(TGFBR1):c.120C>T (p.Leu40=)

gnomAD frequency: 0.00011  dbSNP: rs201267786

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154850	SCV000204532	likely benign	not specified	2014-08-01	criteria provided, single submitter	clinical testing	Leu40Leu in exon 2 of TGFBR1: 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 2/8600 European Amer ican chromosomes and 1/4406 African American chromosomes by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs201267786).
Ambry Genetics	RCV001085490	SCV000319241	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2018-04-17	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
GeneDx	RCV000154850	SCV000514885	likely benign	not specified	2018-03-06	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.
Invitae	RCV001085490	SCV001001806	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2024-01-12	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000861480	SCV001155684	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	TGFBR1: BP4, BP7
Illumina Laboratory Services, Illumina	RCV001166106	SCV001328441	uncertain significance	Loeys-Dietz syndrome 1	2017-04-27	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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001085490	SCV001333556	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2018-01-12	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001085490	SCV001347327	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2018-11-27	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000154850	SCV002766273	benign	not specified	2022-11-06	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000861480	SCV001808806	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000861480	SCV001954602	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000861480	SCV001970544	likely benign	not provided		no assertion criteria provided	clinical testing