ClinVar Miner

Submissions for variant NM_020822.3(KCNT1):c.218T>C (p.Leu73Pro) (rs748537758)

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 RCV000523325 SCV000618159 uncertain significance not provided 2018-10-15 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the KCNT1 gene. The L73P variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The L73P variant is a a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. 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. The L73P variant is not observed in large population cohorts; however, this variant has been detected in two presumably healthy individuals tested at GeneDx (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Ambry Genetics RCV000720687 SCV000851566 uncertain significance Seizures 2017-03-24 criteria provided, single submitter clinical testing The p.L73P variant (also known as c.218T>C), located in coding exon 2 of the KCNT1 gene, results from a T to C substitution at nucleotide position 218. The leucine at codon 73 is replaced by proline, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001316567 SCV001507194 uncertain significance Early infantile epileptic encephalopathy 14; Epilepsy, nocturnal frontal lobe, 5 2020-09-09 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 73 of the KCNT1 protein (p.Leu73Pro). The leucine residue is weakly conserved and there is a moderate physicochemical difference between leucine and proline. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with KCNT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 449770). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KCNT1 protein function. 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.