ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.1421C>T (p.Thr474Ile) (rs199472906)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182021 SCV000234324 pathogenic not provided 2014-10-10 criteria provided, single submitter clinical testing The Thr474Ile mutation in the KCNH2 gene has been published previously in association with LQTS. Tanaka et al. (1997) reported the Thr474Ile mutation co-segregating with LQTS in a Japanese family, and did not detect the mutation in 80 normal individuals.Thr474Ile, which occurs in the S2-S3 region of KCNH2, represents a non-conservative amino acid replacement of a polar Threonine residue with a non-polar Isoleucine residue at a position in the protein that is highly conserved across species throughout evolution. Mutations affecting nearby codons (Asn470Asp, Thr473Asn, Tyr475Cys, Val476Ile) have been reported in association with LQTS, further supporting the functional importance of this region of the protein. Furthermore, Thr474Ile was not detected in up to 600 control chromosomes of African American and Caucasian ethnic groups tested at GeneDx, indicating it is not a common benign polymorphism in these populations. The variant is found in LQT panel(s).
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000057906 SCV000089426 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:9024139;PMID:16432067;PMID:9694858). 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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