ClinVar Miner

Submissions for variant NM_000238.4(KCNH2):c.1128+1849G>A

gnomAD frequency: 0.00001  dbSNP: rs1167016668
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000631560 SCV000752642 uncertain significance Long QT syndrome 2017-12-24 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 62 of the KCNH2 protein (p.Gly21Asp). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. The KCNH2 gene has multiple clinically relevant transcripts. The p.Gly21Asp variant occurs in alternate transcript NM_172057.2, which corresponds to position c.1128+1849G>A in NM_000238.3, the primary transcript listed in the Methods. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly damaging"; Align-GVGD: "Class C0"). This variant has been reported in an individual affected with Long QT syndrome, although a definitive diagnosis was not possible (PMID: 26189708). While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database.

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