ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.707G>T (p.Gly236Val) (rs199472870)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000058247 SCV000234023 uncertain significance not provided 2018-12-11 criteria provided, single submitter clinical testing Although the G236V variant of uncertain significance in the KCNH2 gene has not been reported in any individuals with arrhythmia, it has been identified in at least one individual in a control cohort (Kapa et al., 2009; Giudicessi et al., 2012). Additionally, this variant has been observed in 4/8,646 (0.05%) alleles from individuals of African ancestry in large population cohorts (Lek et al., 2016). The G236V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, in-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect.
Invitae RCV000471386 SCV000543483 uncertain significance Long QT syndrome 2018-07-18 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 236 of the KCNH2 protein (p.Gly236Val). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and valine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with KCNH2-related disease. It has however, been reported as a rare variant in a healthy individual as c.707G>T (PMID: 19841300). ClinVar contains an entry for this variant (Variation ID: 67518). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058247 SCV000089767 not provided not provided no assertion provided literature only This variant has been reported in the following publications (PMID:19841300).

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