ClinVar Miner

Submissions for variant NM_002241.5(KCNJ10):c.179T>C (p.Ile60Thr) (rs759993423)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187814 SCV000241412 uncertain significance not provided 2015-01-16 criteria provided, single submitter clinical testing p.Ile60Thr (ATT>ACT): c.179 T>C in exon 2 of the KCNJ10 gene (NM_002241.4). A variant of unknown significance has been identified in the KCNJ10 gene. The I60T variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The I60T 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 through mammals. In silico analysis predicts this variant is probably 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 CHILD-EPI,EPILEPSY panel(s).
Invitae RCV000646755 SCV000768540 uncertain significance SeSAME syndrome 2017-12-11 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 60 of the KCNJ10 protein (p.Ile60Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs759993423, ExAC 0.002%). This variant has not been reported in the literature in individuals with KCNJ10-related disease. ClinVar contains an entry for this variant (Variation ID: 205826). 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.
Ambry Genetics RCV000716442 SCV000847283 uncertain significance History of neurodevelopmental disorder 2016-07-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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