ClinVar Miner

Submissions for variant NM_181486.4(TBX5):c.618T>G (p.Phe206Leu)

gnomAD frequency: 0.00001  dbSNP: rs533581420
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics, Fulgent Genetics RCV002491145 SCV002776554 uncertain significance Holt-Oram syndrome 2021-08-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV005056228 SCV005701259 uncertain significance Aortic valve disease 2 2024-06-12 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 206 of the TBX5 protein (p.Phe206Leu). This variant is present in population databases (rs533581420, gnomAD 0.003%). This missense change has been observed in individual(s) with long QT and Brugada syndrome (PMID: 33576403). ClinVar contains an entry for this variant (Variation ID: 487603). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TBX5 protein function. Experimental studies have shown that this missense change affects TBX5 function (PMID: 33576403). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000656176 SCV000678370 uncertain significance Wolff-Parkinson-White pattern 2017-07-14 no assertion criteria provided research This variant was identified in an individual with Wolff-Parkinson-White syndrome

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