Submissions for variant NM_003242.6(TGFBR2):c.1159G>A (p.Val387Met)

dbSNP: rs35766612

Total submissions: 21

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037728	SCV000061390	likely benign	not specified	2010-04-23	criteria provided, single submitter	clinical testing
GeneDx	RCV001703884	SCV000250935	likely benign	not provided	2020-08-07	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 32560555, 27879313, 26332594, 26017485, 24941995, 25116393, 16791849, 25637381, 18781618, 23074336, 16571647, 21524434, 17319955, 16928994, 11212236, 24055113)
Ambry Genetics	RCV000249404	SCV000319520	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2018-06-18	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	RCV000288248	SCV000442880	likely benign	Loeys-Dietz syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001094865	SCV000442881	likely benign	Loeys-Dietz syndrome 2	2018-03-19	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.
Illumina Laboratory Services, Illumina	RCV000249404	SCV000442882	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2016-06-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000249404	SCV000559156	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2024-01-31	criteria provided, single submitter	clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000249404	SCV000782370	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2016-11-01	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000768109	SCV000899024	uncertain significance	Loeys-Dietz syndrome 2; Colorectal cancer, hereditary nonpolyposis, type 6	2017-09-19	criteria provided, single submitter	clinical testing	TGFBR2 NM_003242.5 exon 4 p.Val387Met (c.1234G>A): This variant has been reported in the literature in at least 1 individual with suspicion of a syndromic aortopathy; however, the authors of this study suggested that this variant is likely benign (Lerner-Ellis 2014 PMID:24793577). In addition, this variant is present in 0.1% (251/125876) of European individuals, including 1 homozygote in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs35766612). This variant is present in ClinVar (Variation ID:44651). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Color Diagnostics, LLC DBA Color Health	RCV000249404	SCV000902905	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2018-03-16	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000037728	SCV000918310	benign	not specified	2017-09-05	criteria provided, single submitter	clinical testing
Mendelics	RCV000345619	SCV001136356	benign	Marfan syndrome	2019-05-28	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001703884	SCV001159277	likely benign	not provided	2023-04-18	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000249404	SCV001333525	benign	Familial thoracic aortic aneurysm and aortic dissection	2019-01-15	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001703884	SCV002544777	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	TGFBR2: PP3, BS1
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002277125	SCV002566150	benign	Ehlers-Danlos syndrome	2020-12-11	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224121	SCV003920555	uncertain significance	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 exon 4 p.Val387Met (c.1234G>A): This variant has been reported in the literature in at least 1 individual with suspicion of a syndromic aortopathy; however, the authors of this study suggested that this variant is likely benign (Lerner-Ellis 2014 PMID:24793577). In addition, this variant is present in 0.1% (251/125876) of European individuals, including 1 homozygote in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs35766612). This variant is present in ClinVar (Variation ID:44651). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
CSER _CC_NCGL, University of Washington	RCV000148893	SCV000190639	uncertain significance	Congenital aneurysm of ascending aorta	2014-06-01	no assertion criteria provided	research
GenomeConnect, ClinGen	RCV000509502	SCV000607367	not provided	Loeys-Dietz syndrome; Thoracic aortic aneurysm; Thoracic aortic dissection		no assertion provided	phenotyping only	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000288248	SCV000692265	uncertain significance	Loeys-Dietz syndrome	2016-05-17	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003904922	SCV004726282	likely benign	TGFBR2-related disorder	2019-07-11	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).