ClinVar Miner

Submissions for variant NM_001077653.2(TBX20):c.994C>T (p.Pro332Ser)

gnomAD frequency: 0.00003  dbSNP: rs201431768
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Klaassen Lab, Charite University Medicine Berlin RCV000853151 SCV000995864 uncertain significance Primary dilated cardiomyopathy 2019-07-03 criteria provided, single submitter research
GeneDx RCV001552165 SCV001772810 uncertain significance not provided 2023-01-27 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function
Labcorp Genetics (formerly Invitae), Labcorp RCV001552165 SCV002137333 uncertain significance not provided 2023-12-13 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 332 of the TBX20 protein (p.Pro332Ser). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 31568572). ClinVar contains an entry for this variant (Variation ID: 691824). 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 TBX20 protein function with a negative predictive value of 80%. 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.
Ambry Genetics RCV002381907 SCV002688855 uncertain significance Cardiovascular phenotype 2023-04-28 criteria provided, single submitter clinical testing The p.P332S variant (also known as c.994C>T), located in coding exon 7 of the TBX20 gene, results from a C to T substitution at nucleotide position 994. The proline at codon 332 is replaced by serine, an amino acid with similar properties. This variant has been detected in an individual with pediatric-onset dilated cardiomyopathy; however details were limited (Kühnisch J et al. Clin. Genet., 2019 Sep). This amino acid position is poorly conserved in available vertebrate species, and serine is the reference amino acid in other 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.

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