ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.398T>C (p.Met133Thr) (rs794728353)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181755 SCV000234058 uncertain significance not provided 2013-04-03 criteria provided, single submitter clinical testing p.Met133Thr (ATG>ACG): c.398 T>C in exon 3 of the KCNH2 gene (NM_000238.2). The Met133Thr variant in the KCNH2 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Met133Thr results in a non-conservative amino acid substitution of a non-polar Methionine with a polar Threonine at a position that is not conserved across species. Mutations in nearby codons (Glu130Lys, Pro141Leu) have been reported in association with LQTS, supporting the functional importance of this region of the protein. The Met133Thr variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. With the clinical and molecular information available at this time, we cannot definitively determine if Met133Thr is a disease-causing mutation or a rare benign variant. The variant is found in LQT panel(s).
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000238963 SCV000296887 uncertain significance Long QT syndrome 2 2015-08-07 criteria provided, single submitter clinical testing

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