ClinVar Miner

Submissions for variant NM_002241.5(KCNJ10):c.652C>T (p.Leu218Phe) (rs558502886)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187817 SCV000241415 uncertain significance not specified 2016-09-19 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the KCNJ10 gene. The L218F variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The L218F variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project and was not observed with any significant frequency in the 1000 Genomes Project. The L218F variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and 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 variant or a rare benign variant.
Fulgent Genetics,Fulgent Genetics RCV000764990 SCV000896169 uncertain significance Enlarged vestibular aqueduct; Pendred syndrome; SeSAME syndrome 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000810914 SCV000951154 uncertain significance SeSAME syndrome 2018-11-29 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 218 of the KCNJ10 protein (p.Leu218Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be heterozygous in an individual with severe epilepsy and profound developmental delay (PMID: 28747464). It was inherited from an unaffected parent and this reported individual also had a second variant that is pathogenic in KCNT1 gene (c.862G>A(p.Gly288Ser)). ClinVar contains an entry for this p.Leu218Phe variant (Variation ID: 205829). This variant has been reported to affect KCNJ10 protein function in both heterozygous and homozygous states (PMID: 28747464). 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.