ClinVar Miner

Submissions for variant NM_181486.4(TBX5):c.1124G>A (p.Arg375Gln)

gnomAD frequency: 0.00001  dbSNP: rs1486871388
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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 RCV001039114 SCV001202626 uncertain significance Aortic valve disease 2 2019-04-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 375 of the TBX5 protein (p.Arg375Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TBX5-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
GeneDx RCV001759948 SCV001991525 uncertain significance not provided 2019-08-12 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002434449 SCV002748644 uncertain significance Cardiovascular phenotype 2022-09-29 criteria provided, single submitter clinical testing The p.R375Q variant (also known as c.1124G>A), located in coding exon 8 of the TBX5 gene, results from a G to A substitution at nucleotide position 1124. The arginine at codon 375 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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