ClinVar Miner

Submissions for variant NM_006920.6(SCN1A):c.4522C>A (p.Pro1508Thr) (rs796053021)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188963 SCV000242594 uncertain significance not provided 2017-09-19 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SCN1A gene. The P1519T variant has previously reported in an individual with Dravet syndrome, however parental testing was not reported (Moehring et al., 2013). The P1519T variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P1519T 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 alters a conserved position predicted to be within the cytoplasmic loop between third and fourth homologous domains. In silico analysis predicts this variant is probably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000818881 SCV000959518 uncertain significance Early infantile epileptic encephalopathy 2018-11-08 criteria provided, single submitter clinical testing This sequence change replaces proline with threonine at codon 1519 of the SCN1A protein (p.Pro1519Thr). The proline residue is highly conserved and there is a small physicochemical difference between proline and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with Dravet syndrome (PMID: 23398550). ClinVar contains an entry for this variant (Variation ID: 206838). 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.

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.