ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.1264G>A (p.Ala422Thr) (rs199472895)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181786 SCV000234089 pathogenic not provided 2012-07-31 criteria provided, single submitter clinical testing p.Ala422Thr (GCT>ACT):c.1264 G>A in exon 6 of the KCNH2 gene (NM_000238.2)The Ala422Thr mutation in the KCNH2 gene has been reported in association with LQTS (Tester D et al., 2005; Anderson C et al., 2006). Tester et al. identified Ala422Thr in one patient with LQTS and it was absent from 1,400 reference alleles tested. Functional studies performed report Ala422Thr utilizes a dominant mechanism leading to a loss of function of the ion channel (Anderson C et al., 2006). Ala422Thr results in a non-conservative amino acid substitution of a non-polar Alanine residue with a polar Threonine residue. Also, mutations in nearby codons (Tyr420Cys, Thr421Met, Pro426His, Tyr427Cys) have been reported in association with LQTS, further supporting the functional importance of this region of the protein.In summary, Ala422Thr in the KCNH2 gene is interpreted as a disease-causing mutation. The variant is found in LQT panel(s).
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000057881 SCV000089401 not provided Congenital long QT syndrome no assertion provided literature only This variant has been reported as associated with Long QT syndrome in the following publications (PMID:15242738;PMID:15840476;PMID:16432067;PMID:22580281). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.

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