ClinVar Miner

Submissions for variant NM_181486.4(TBX5):c.1162G>A (p.Glu388Lys)

gnomAD frequency: 0.00007  dbSNP: rs139371720
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000457110 SCV000552101 uncertain significance Aortic valve disease 2 2023-07-10 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with clinical features of dilated cardiomyopathy (PMID: 31983221). 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. 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) performed at Invitae indicates that this missense variant is not expected to disrupt TBX5 protein function. ClinVar contains an entry for this variant (Variation ID: 411098). This variant is also known as chr12:g.114793732C>T. This variant is present in population databases (rs139371720, gnomAD 0.005%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 388 of the TBX5 protein (p.Glu388Lys).
Ambry Genetics RCV002356697 SCV002623431 uncertain significance Cardiovascular phenotype 2022-01-31 criteria provided, single submitter clinical testing The p.E388K variant (also known as c.1162G>A), located in coding exon 8 of the TBX5 gene, results from a G to A substitution at nucleotide position 1162. The glutamic acid at codon 388 is replaced by lysine, an amino acid with similar properties. This alteration has been reported in a dilated cardiomyopathy (DCM) cohort with limited clinical details (Mazzarotto F et al. Circulation, 2020 02;141:387-398). This amino acid position is well conserved in available 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.
CeGaT Center for Human Genetics Tuebingen RCV003392284 SCV004131997 uncertain significance not provided 2022-07-01 criteria provided, single submitter clinical testing

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