Submissions for variant NM_003242.6(TGFBR2):c.1657T>A (p.Ser553Thr)

gnomAD frequency: 0.00115  dbSNP: rs112215250

Total submissions: 20

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000152014	SCV000200582	uncertain significance	not specified	2017-01-10	criteria provided, single submitter	clinical testing	proposed classification - variant undergoing re-assessment, contact laboratory
GeneDx	RCV000152014	SCV000250957	benign	not specified	2017-11-22	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.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000239196	SCV000296974	likely benign	Loeys-Dietz syndrome	2015-11-16	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000241715	SCV000318116	benign	Familial thoracic aortic aneurysm and aortic dissection	2016-04-06	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.
Illumina Laboratory Services, Illumina	RCV000337404	SCV000442904	likely benign	Marfan syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000241715	SCV000442905	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001094793	SCV000442906	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000241715	SCV000559155	benign	Familial thoracic aortic aneurysm and aortic dissection	2025-02-03	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587520	SCV000698197	benign	not provided	2017-04-17	criteria provided, single submitter	clinical testing	Variant summary: The TGFBR2 c.1657T>A (p.Ser553Thr) variant involves the alteration of a conserved nucleotide and 3/5 in silico tools predict a damaging outcome. This variant was found in 170/121354 control chromosomes (2 homozygotes) at a frequency of 0.0014009, which is approximately 1121 times the estimated maximal expected allele frequency of a pathogenic TGFBR2 variant (0.0000013), suggesting this variant is likely a benign polymorphism. Multiple publications have cited the variant in affected individuals. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant with conflicting classifications "uncertain significance" or "likely benign." However, it needs to be noted that many databases/clinical diagnostic laboratories that classified the variant as "uncertain significance" were performed before ExAC data was availalbe. In addition, ClinVar-Partners does state that the variant did not segregate with disease in one family. Therefore, taking all available lines of evidence into consideration, the variant of interest has been classified as Benign.
Eurofins Ntd Llc (ga)	RCV000152014	SCV000703465	benign	not specified	2016-12-09	criteria provided, single submitter	clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000680614	SCV000808044	likely benign	Connective tissue disorder	2018-06-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000241715	SCV000910746	benign	Familial thoracic aortic aneurysm and aortic dissection	2018-03-15	criteria provided, single submitter	clinical testing
Mendelics	RCV000337404	SCV001136358	benign	Marfan syndrome	2019-05-28	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002277295	SCV002566159	likely benign	Ehlers-Danlos syndrome	2021-10-21	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000587520	SCV002821170	likely benign	not provided	2025-01-01	criteria provided, single submitter	clinical testing	TGFBR2: BS1
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000241715	SCV003838138	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2022-07-22	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000587520	SCV005876112	likely benign	not provided	2024-01-18	criteria provided, single submitter	clinical testing
Molecular Genetics, Royal Melbourne Hospital	RCV001094793	SCV005900391	likely benign	Loeys-Dietz syndrome 2	2024-05-02	criteria provided, single submitter	clinical testing
CSER _CC_NCGL, University of Washington	RCV000148891	SCV000190637	likely benign	Congenital aneurysm of ascending aorta	2014-06-01	no assertion criteria provided	research
PreventionGenetics, part of Exact Sciences	RCV003935259	SCV004747727	benign	TGFBR2-related disorder	2020-10-05	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).