ClinVar Miner

Submissions for variant NM_000891.3(KCNJ2):c.913A>G (p.Thr305Ala)

dbSNP: rs199473387
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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 RCV001068766 SCV001233898 likely pathogenic Andersen Tawil syndrome; Short QT syndrome type 3 2023-06-04 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Thr305 amino acid residue in KCNJ2. Other variant(s) that disrupt this residue have been observed in individuals with KCNJ2-related conditions (PMID: 17324964, 22589293, 24383070), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this missense change affects KCNJ2 function (PMID: 17341397). 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 expected to disrupt KCNJ2 protein function. ClinVar contains an entry for this variant (Variation ID: 67591). This missense change has been observed in individuals with catecholaminergic polymorphic ventricular tachycardia (CPVT) and Andersen-Tawil syndrome (PMID: 17341397, 27145478). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 305 of the KCNJ2 protein (p.Thr305Ala).
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust RCV001841764 SCV000089856 not provided Cardiac arrhythmia no assertion provided literature only This variant has been reported as associated with Arrhythmia in the following publications (PMID:17341397). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital RCV000678809 SCV000804993 pathogenic Andersen Tawil syndrome 2015-08-28 no assertion criteria provided clinical testing

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