Submissions for variant NM_004612.4(TGFBR1):c.415A>G (p.Ile139Val)

gnomAD frequency: 0.00022  dbSNP: rs148176750

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154441	SCV000204110	uncertain significance	not specified	2016-02-11	criteria provided, single submitter	clinical testing	proposed classification - variant undergoing re-assessment, contact laboratory
Invitae	RCV000229273	SCV000288620	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2023-12-23	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000229273	SCV000475612	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000328066	SCV000475613	likely benign	Loeys-Dietz syndrome 1	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000384899	SCV000475614	likely benign	Loeys-Dietz syndrome	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000766901	SCV000514886	likely benign	not provided	2020-11-24	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24793577)
Ambry Genetics	RCV000229273	SCV000739750	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2018-08-14	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.
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000229273	SCV000782356	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2016-11-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000154441	SCV000918307	likely benign	not specified	2017-10-13	criteria provided, single submitter	clinical testing	Variant summary: The c.415A>G (p.Ile139Val) in TGFBR1 gene is a missense change that involves the alteration of a non- conserved nucleotide and 5/4 in silico tools predict benign outcome. The variant was observed in the control datasets of the ExAC and gnomAD at a frequency of 0.00025 (24/121346 and 62/245812 chrs tested, including 1 homozygote). The observed frequency exceeds the maximal expected allele frequency for a pathogenic variant in this gene (0.000002). The variant has been identified in 1 individual with suspected MSF/LDS or TAAD, without strong evidence for causality (Lerner-Ellis_2014). In addition, one clinical laboratory reports co-occurrence of this variant with unspecified pathogenic cardiogenetic variant with disclosure that segregation analysis was not performed. Although several reputable databases/diagnostic centers classified the variant of interest as VUS/Likely Benign, by applying ACMG rules the variant was classified as Likely Benign.
Color Diagnostics, LLC DBA Color Health	RCV000229273	SCV001345186	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2018-11-08	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000766901	SCV001500556	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	TGFBR1: BP4, BS2