Submissions for variant NM_004612.4(TGFBR1):c.1152C>T (p.Leu384=)

gnomAD frequency: 0.00207  dbSNP: rs115324990

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038236	SCV000061904	benign	not specified	2012-06-22	criteria provided, single submitter	clinical testing	Leu384Leu in Exon 07 of TGFBR1: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence and has been identified in 0.9% (32/3738) of Afr ican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs115324990).
GeneDx	RCV000038236	SCV000250856	benign	not specified	2014-10-22	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.
Ambry Genetics	RCV000245235	SCV000319250	benign	Familial thoracic aortic aneurysm and aortic dissection	2015-12-02	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Invitae	RCV000245235	SCV000559251	benign	Familial thoracic aortic aneurysm and aortic dissection	2024-01-25	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590186	SCV000698476	benign	not provided	2016-08-22	criteria provided, single submitter	clinical testing	Variant summary: The TGFBR1 c.1152C>T (p.Leu384Leu) variant causes a synonymous change involving a non-conserved nucleotide with 5/5 splice prediction tools predicting no significant impact on splicing or ESE binding, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 109/121370 (1/1113), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic TGFBR1 variant of 1/769230, suggesting this variant is likely a benign polymorphism. In addition, multiple reputable clinical laboratories cite the variant as "benign." Therefore, the variant of interest has been classified as Benign.
Color Diagnostics, LLC DBA Color Health	RCV000245235	SCV000903641	benign	Familial thoracic aortic aneurysm and aortic dissection	2018-03-08	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000590186	SCV001473983	benign	not provided	2021-04-29	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003315557	SCV004015611	benign	Multiple self-healing squamous epithelioma	2023-07-07	criteria provided, single submitter	clinical testing