ClinVar Miner

Submissions for variant NM_003239.4(TGFB3):c.873G>A (p.Pro291=) (rs370006165)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000618845 SCV000737736 likely benign Cardiovascular phenotype 2016-10-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Synonymous alterations with insufficient evidence to classify as benign
GeneDx RCV000435962 SCV000532589 likely benign not specified 2017-05-04 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.
Integrated Genetics/Laboratory Corporation of America RCV000435962 SCV000920304 likely benign not specified 2018-02-20 criteria provided, single submitter clinical testing Variant summary: TGFB3 c.873G>A alters a non-conserved nucleotide resulting in a synonymous change. Computational tools predict that the variant may alter splicing. However, these predictions have yet to be confirmed by functional studies. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 19-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in TGFB3 causing Arrhythmia phenotype (0.002 vs 1e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. To our knowledge, no occurrence of c.873G>A in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely benign, and one laboratory classified the variant as uncertain significance. Based on the available evidence, the variant was classified as likely benign.
Invitae RCV000232643 SCV000287914 uncertain significance Loeys-Dietz syndrome 4 2016-01-10 criteria provided, single submitter clinical testing

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