ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.2312A>G (p.His771Arg) (rs1060500659)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000469290 SCV000543414 uncertain significance Long QT syndrome 2018-10-24 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 771 of the KCNH2 protein (p.His771Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual referred for long QT syndrome testing and has been found to segregate with long QT syndrome in one family (PMID: 23098067, Invitae). This variant identified in the KCNH2 gene is located in the cytoplasmic cyclic nucleotide binding region of the resulting protein (PMID: 19841300), but it is unclear how this variant impacts the function of this protein. 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: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change that is not present in general population databases and has been found in a potentially affected individual in the literature. In the absence of any functional or segregation data it has been classified as a Variant of Uncertain Significance.

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