ClinVar Miner

Submissions for variant NM_006073.4(TRDN):c.727A>G (p.Thr243Ala)

gnomAD frequency: 0.00009  dbSNP: rs376208769
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002524465 SCV001229738 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1 2024-01-22 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 243 of the TRDN protein (p.Thr243Ala). This variant is present in population databases (rs376208769, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with TRDN-related conditions. ClinVar contains an entry for this variant (Variation ID: 355219). 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 TRDN 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 RCV002379245 SCV002672761 likely benign Cardiovascular phenotype 2024-06-04 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
New York Genome Center RCV002467765 SCV002764333 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 5 2021-08-06 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002487556 SCV002792268 uncertain significance Catecholaminergic polymorphic ventricular tachycardia 1; Catecholaminergic polymorphic ventricular tachycardia 5 2021-10-13 criteria provided, single submitter clinical testing
GeneDx RCV003105882 SCV003761725 uncertain significance not provided 2023-01-30 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function

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