ClinVar Miner

Submissions for variant NM_002241.5(KCNJ10):c.148C>T (p.Leu50Phe) (rs773510302)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725019 SCV000333267 uncertain significance not provided 2015-08-12 criteria provided, single submitter clinical testing
GeneDx RCV000725019 SCV000522187 uncertain significance not provided 2016-12-23 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the KCNJ10 gene. The L50F variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The L50F 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). This substitution occurs at a position that is conserved in mammals. However, the L50F variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. 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 RCV000646753 SCV000768538 uncertain significance SeSAME syndrome 2018-02-10 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 50 of the KCNJ10 protein (p.Leu50Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is present in population databases (rs773510302, 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: 282077). 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: "Tolerated"; PolyPhen-2: "Probably 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.

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