ClinVar Miner

Submissions for variant NM_001135599.3(TGFB2):c.703G>C (p.Val235Leu) (rs10482810)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000196984 SCV000250836 benign not specified 2017-02-22 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.
Invitae RCV000986554 SCV000287902 benign Holt-Oram syndrome 2020-12-01 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000196984 SCV000309501 benign not specified criteria provided, single submitter clinical testing
Ambry Genetics RCV000617048 SCV000319480 likely benign Cardiovascular phenotype 2019-04-16 criteria provided, single submitter clinical testing In silico models in agreement (benign);Subpopulation frequency in support of benign classification
Illumina Clinical Services Laboratory,Illumina RCV000415676 SCV000354244 likely benign Loeys-Dietz syndrome 4 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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000415676 SCV000605367 benign Loeys-Dietz syndrome 4 2020-07-02 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000514721 SCV000610833 likely benign not provided 2017-03-28 criteria provided, single submitter clinical testing
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000415676 SCV000782351 benign Loeys-Dietz syndrome 4 2016-11-01 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000196984 SCV000858025 likely benign not specified 2017-11-29 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000143953 SCV000900955 benign Familial thoracic aortic aneurysm and aortic dissection 2019-03-20 criteria provided, single submitter clinical testing
Mendelics RCV000986554 SCV001135573 likely benign Holt-Oram syndrome 2019-05-28 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000196984 SCV001362849 likely benign not specified 2019-08-12 criteria provided, single submitter clinical testing Variant summary: TGFB2 c.619G>C (p.Val207Leu) results in a conservative amino acid change located in the TGF-beta propeptide domain (IPR001111) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0033 in 251286 control chromosomes, predominantly at a frequency of 0.005 within the Non-Finnish European subpopulation in the gnomAD database, including 5 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 400 fold of the estimated maximal expected allele frequency for a pathogenic variant in TGFB2 causing Aortopathy phenotype (1.3e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. c.619G>C has been reported in the literature in individuals affected with aortic root dilation, vascular anomalies and familial abdominal aortic aneurysm (Disha_2017, vandeLuijtgaarden_2015, Mattassi_2018) without strong evidence of causality. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Ten submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (9x Likely benign/benign and 1x uncertain significance). Based on the evidence outlined above, the variant was classified as likely benign.
Blueprint Genetics RCV000143953 SCV000188833 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2013-10-11 no assertion criteria provided clinical testing
Knight Diagnostic Laboratories, Oregon Health and Sciences University RCV000415676 SCV000493807 uncertain significance Loeys-Dietz syndrome 4 2016-03-30 no assertion criteria provided clinical testing

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