Submissions for variant NM_003242.6(TGFBR2):c.571G>A (p.Val191Ile)

gnomAD frequency: 0.00039  dbSNP: rs56105708

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000125486	SCV000168938	benign	not specified	2013-07-02	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.
Invitae	RCV000228364	SCV000287924	benign	Familial thoracic aortic aneurysm and aortic dissection	2024-01-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000228364	SCV000319179	benign	Familial thoracic aortic aneurysm and aortic dissection	2016-03-21	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.
Illumina Laboratory Services, Illumina	RCV000352880	SCV000442844	likely benign	Loeys-Dietz syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000228364	SCV000442845	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000313129	SCV000442846	likely benign	Loeys-Dietz syndrome 2	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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589501	SCV000698198	benign	not provided	2017-08-16	criteria provided, single submitter	clinical testing	Variant summary: The TGFBR2 c.571G>A (p.Val191Ile) variant involves the alteration of a conserved nucleotide, resulting in a missense change. 4/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 196 of 121384 control chromosomes (2 homozygotes) of all ethnicities sampled in ExAC, but was predominantly observed in the East Asian subpopulation at a frequency of 0.018741 (162/8644; 2 homozygotes). This frequency is about 5997 times the estimated maximal expected allele frequency of a pathogenic TGFBR2 variant (0.0000031), strongly suggesting this is likely a benign polymorphism found primarily in the populations of East Asian origin. The variant is referred to as a polymorphism in the literature and has been used as a SNP in an association study. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000228364	SCV000901781	benign	Familial thoracic aortic aneurysm and aortic dissection	2016-02-02	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000228364	SCV000903047	benign	Familial thoracic aortic aneurysm and aortic dissection	2018-03-08	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002498604	SCV002807067	likely benign	Loeys-Dietz syndrome 2; Malignant tumor of esophagus; Colorectal cancer, hereditary nonpolyposis, type 6	2022-01-19	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000589501	SCV004562170	likely benign	not provided	2023-04-07	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000589501	SCV001977677	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000589501	SCV001978316	likely benign	not provided		no assertion criteria provided	clinical testing