ClinVar Miner

Submissions for variant NM_153033.4(KCTD7):c.403G>A (p.Gly135Arg) (rs781725855)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000325172 SCV000469808 uncertain significance Progressive myoclonic epilepsy 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000413798 SCV000492108 uncertain significance not provided 2016-11-22 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the KCTD7 gene. The G135R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The G135R variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G135R 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 across species. However, 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 variant or a rare benign variant.
Invitae RCV000645672 SCV000767423 uncertain significance Epilepsy, progressive myoclonic 3 2019-01-06 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 135 of the KCTD7 protein (p.Gly135Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs781725855, ExAC 0.01%). This variant has not been reported in the literature in individuals with KCTD7-related disease. ClinVar contains an entry for this variant (Variation ID: 360587). 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"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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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