ClinVar Miner

Submissions for variant NM_000238.4(KCNH2):c.131G>A (p.Cys44Tyr)

dbSNP: rs199473489
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001581933 SCV001818098 likely pathogenic not provided 2021-07-23 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function This variant is associated with the following publications: (PMID: 23631430)
Labcorp Genetics (formerly Invitae), Labcorp RCV003533011 SCV004295079 uncertain significance Long QT syndrome 2023-04-28 criteria provided, single submitter clinical testing 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. This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 44 of the KCNH2 protein (p.Cys44Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of long QT syndrome (PMID: 23631430; Invitae). ClinVar contains an entry for this variant (Variation ID: 1214199). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects KCNH2 function (PMID: 35688148). This variant disrupts the p.Cys44 amino acid residue in KCNH2. Other variant(s) that disrupt this residue have been observed in individuals with KCNH2-related conditions (PMID: 27816319; Invitae), which suggests that this may be a clinically significant amino acid residue.

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