ClinVar Miner

Submissions for variant NM_000238.4(KCNH2):c.1919T>G (p.Phe640Cys)

dbSNP: rs1801154920
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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 RCV001350204 SCV001544586 uncertain significance Long QT syndrome 2020-09-20 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 variant disrupts the p.Phe640 amino acid residue in KCNH2. Other variant(s) that disrupt this residue have been observed in individuals with KCNH2-related conditions (PMID: 22949429), which suggests that this may be a clinically significant amino acid residue. This variant has not been reported in the literature in individuals with KCNH2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with cysteine at codon 640 of the KCNH2 protein (p.Phe640Cys). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and cysteine.

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