ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.1280A>C (p.Tyr427Ser) (rs199472897)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000246613 SCV000319053 likely pathogenic Cardiovascular phenotype 2013-10-30 criteria provided, single submitter clinical testing Rarity in general population databases (dbsnp, esp, 1000 genomes);Well-characterized mutation at same position;In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Integrated Genetics/Laboratory Corporation of America RCV000246613 SCV000696017 likely pathogenic Cardiovascular phenotype 2016-11-07 criteria provided, single submitter clinical testing Variant summary: The KCNH2 c.1280A>C (p.Tyr427Ser) variant involves the alteration of a highly conserved nucleotide and is located in the ion transport domain at S1-S4 transmembrane region (InterPro, Itoh_2016). 5/5 in silico tools predict a damaging outcome for this variant. This variant is absent in 125938 control chromosomes, including the large and broad populations from ExAC. This variant has been reported as a pathogenic variant in literature found in at least two LQTS families; and in one family, the variant was found to be paternally inherited (Tester_2005, Kapa_2009, Giudicessi_2012, Itoh_2010, Itoh_2016). Other missense variants such as p.Tyr427His (PMIDs: 16414944, 16922724, and 22581653) and p.Tyr427Cys (PMIDs: 19716085 and 22581653) have also been reported in this codon, indicating that the codon is in a mutational hot-spot. One clinical diagnostic laboratory has classified this variant as likely pathogenic. Taken together, this variant is classified as Likely Pathogenic.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000057885 SCV000089405 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:15840476;PMID:19841300). 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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