ClinVar Miner

Submissions for variant NM_003238.6(TGFB2):c.356C>T (p.Pro119Leu)

gnomAD frequency: 0.00047  dbSNP: rs149533093
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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000196866 SCV000250839 likely benign not specified 2018-01-05 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.
Illumina Laboratory Services,Illumina RCV000415640 SCV000354238 benign Loeys-Dietz syndrome 4 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae RCV000415640 SCV000548101 likely benign Loeys-Dietz syndrome 4 2021-12-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV000621239 SCV000739695 uncertain significance Cardiovascular phenotype 2018-08-27 criteria provided, single submitter clinical testing The p.P119L variant (also known as c.356C>T), located in coding exon 2 of the TGFB2 gene, results from a C to T substitution at nucleotide position 356. The proline at codon 119 is replaced by leucine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and leucine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769556 SCV000900952 likely benign Familial thoracic aortic aneurysm and aortic dissection 2018-09-04 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001093207 SCV001250069 uncertain significance not provided 2020-01-01 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000415640 SCV001366540 likely benign Loeys-Dietz syndrome 4 2019-05-06 criteria provided, single submitter clinical testing This variant was classified as: Likely benign. The following ACMG criteria were applied in classifying this variant: PP4,BP4,BP6.
Baylor Genetics RCV000415640 SCV001525606 uncertain significance Loeys-Dietz syndrome 4 2018-03-11 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000196866 SCV002074422 likely benign not specified 2022-01-24 criteria provided, single submitter clinical testing Variant summary: TGFB2 c.356C>T (p.Pro119Leu) results in a non-conservative amino acid change located in the TGF-beta, propeptide domain (IPR001111) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00039 in 238938 control chromosomes. The observed variant frequency is approximately 311 fold of the estimated maximal expected allele frequency for a pathogenic variant in TGFB2 causing Aortopathy phenotype (1.3e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.356C>T in individuals affected with Aortopathy/Loeys-Dietz Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Ten clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (likely benign/benign, n=5; VUS, n=5). Based on the evidence outlined above, the variant was classified as likely benign.
Genome Diagnostics Laboratory,The Hospital for Sick Children RCV002277545 SCV002566117 likely benign Ehlers-Danlos syndrome 2019-06-01 criteria provided, single submitter clinical testing
Knight Diagnostic Laboratories, Oregon Health and Sciences University RCV000415640 SCV000493806 uncertain significance Loeys-Dietz syndrome 4 2015-10-23 no assertion criteria provided clinical testing
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000583868 SCV000692266 uncertain significance Aortic aneurysm 2017-02-16 no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001093207 SCV001927821 likely benign not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001093207 SCV001957638 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001093207 SCV001970234 likely benign not provided no assertion criteria provided clinical testing

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