ClinVar Miner

Submissions for variant NM_000192.3(TBX5):c.1115C>T (p.Ser372Leu) (rs143068551)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000621377 SCV000736123 likely benign Cardiovascular phenotype 2017-12-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Subpopulation frequency in support of benign classification,In silico models in agreement (benign)
Invitae RCV000532471 SCV000659012 uncertain significance Aortic valve disease 2 2017-01-26 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 372 of the TBX5 protein (p.Ser372Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs143068551, ExAC 0.03%). This variant has been reported in individuals affected with bicuspid aortic valve, atrial fibrillation, or tetralogy of Fallot (PMID: 25260786, 26762269, 25263169). An experimental study has shown that this missense change has higher activity than wild-type protein in vitro (PMID: 25263169). In summary, this variant is a rare missense change with increased protein function. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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