ClinVar Miner

Submissions for variant NM_004588.5(SCN2B):c.625_626delinsCC (p.Asn209Pro) (rs1064796044)

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 RCV000480760 SCV000572426 uncertain significance not specified 2016-12-09 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SCN2B gene. The c.625_626delAAinsCC variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant 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 c.625_626delAAinsCC variant results in a non-conservative amino acid substitution of an Asparagine residue for a Proline residue (N209P), which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is only conserved through mammals and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Invitae RCV001206528 SCV001377839 uncertain significance Atrial fibrillation, familial, 14 2019-06-21 criteria provided, single submitter clinical testing This sequence change replaces asparagine with proline at codon 209 of the SCN2B protein (p.Asn209Pro). The asparagine residue is highly conserved and there is a moderate physicochemical difference between asparagine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with epilepsy (PMID: 10976944). ClinVar contains an entry for this variant (Variation ID: 422854). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly 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.

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.