Submissions for variant NM_003242.6(TGFBR2):c.1119G>A (p.Met373Ile)

gnomAD frequency: 0.00130  dbSNP: rs35719192

Total submissions: 26

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000756779	SCV000168941	likely benign	not provided	2020-11-24	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 17344846, 16928994, 9395234, 23884466, 27153395, 18781618)
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000152008	SCV000200573	likely benign	not specified	2011-06-15	criteria provided, single submitter	clinical testing	This variant has previously been reported in the literature in an individual wit h clinical features of Loeys-Dietz syndrome; however, the variant was also found in 1/200 control chromosomes (Loeys 2006) and in the reportedly unaffected pare nt of a proband in our laboratory. In addition, this residue is not highly conse rved through different species, which raises the possibility that amino acid cha nges at this position may be tolerated. Therefore, this variant is likely to be benign.
PreventionGenetics, part of Exact Sciences	RCV000152008	SCV000309515	likely benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000251845	SCV000317806	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2019-01-23	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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	RCV000251845	SCV000442877	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000327596	SCV000442878	likely benign	Marfan syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000030541	SCV000442879	likely benign	Loeys-Dietz syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000251845	SCV000559151	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2024-01-31	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000152008	SCV000705827	likely benign	not specified	2017-02-06	criteria provided, single submitter	clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000251845	SCV000782368	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2016-11-01	criteria provided, single submitter	clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000680612	SCV000808042	likely benign	Connective tissue disorder	2018-06-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000756779	SCV000884689	benign	not provided	2023-11-01	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000251845	SCV000911064	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2018-03-16	criteria provided, single submitter	clinical testing
Mendelics	RCV000327596	SCV001136355	likely benign	Marfan syndrome	2019-05-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000756779	SCV001153824	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	TGFBR2: BS1
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000251845	SCV001333524	benign	Familial thoracic aortic aneurysm and aortic dissection	2019-03-25	criteria provided, single submitter	clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000152008	SCV001433239	benign	not specified	2019-01-14	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002277108	SCV002566149	likely benign	Ehlers-Danlos syndrome	2019-05-01	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003227612	SCV003924165	likely benign	Loeys-Dietz syndrome 2; Malignant tumor of esophagus; Colorectal cancer, hereditary nonpolyposis, type 6	2021-03-30	criteria provided, single submitter	clinical testing	TGFBR2 NM_003242.5 exon 4 p.Met373Ile (c.1119G>A): This variant has been reported in the literature in one individual with Loeys-Dietz syndrome (Frischmeyer-Guerrerio 2013 PMID:23884466). However, this variant isalso present in 0.3% (47/13666) of Latino alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/3-30672302-G-A?dataset=gnomad_r3) and is present in ClinVar, with several labs classifying this variant as benign or likely benign (Variation ID:36859). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant suggests that this variant does not cause disease, but requires further evidence. Therefore this variant is classified as likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000030541	SCV000053212	benign	Loeys-Dietz syndrome	2015-02-23	no assertion criteria provided	clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000030541	SCV000257744	uncertain significance	Loeys-Dietz syndrome	2015-06-17	flagged submission	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000152008	SCV001548960	benign	not specified		no assertion criteria provided	clinical testing	LB/B > 4 on ClinVar or LB/B > 2 Rep
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000756779	SCV001798991	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000756779	SCV001808374	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000756779	SCV001932938	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000756779	SCV001968116	likely benign	not provided		no assertion criteria provided	clinical testing