ClinVar Miner

Submissions for variant NM_002241.5(KCNJ10):c.688C>T (p.Arg230Trp) (rs149615470)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187809 SCV000241407 uncertain significance not specified 2015-07-10 criteria provided, single submitter clinical testing p.Arg230Trp (CGG>TGG): c.688 C>T in exon 2 of the KCNJ10 gene (NM_002241.4)A variant of unknown significance has been identified in the KCNJ10 gene. The R230W variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The R230W variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, but the 1000 Genomes Project reports R230W was observed in 1/186 (0.5%) alleles from individuals of Finnish background. The R230W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals; however, this position is not conserved in more distantly related species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.The variant is found in EPILEPSY panel(s).
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000726422 SCV000344519 uncertain significance not provided 2016-09-15 criteria provided, single submitter clinical testing
Invitae RCV000704721 SCV000833681 uncertain significance SeSAME syndrome 2018-12-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 230 of the KCNJ10 protein (p.Arg230Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs149615470, ExAC 0.03%). This variant has not been reported in the literature in individuals with KCNJ10-related disease. ClinVar contains an entry for this variant (Variation ID: 205821). 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: "Benign"; 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.

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