ClinVar Miner

Submissions for variant NM_014191.4(SCN8A):c.5879G>A (p.Arg1960Gln) (rs369346315)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000726306 SCV000242927 uncertain significance not provided 2018-02-21 criteria provided, single submitter clinical testing The R1960Q variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed with any significant frequency in approximately 6,000 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The R1960Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution alters a position conserved in mammals within the cytoplasmic topological domain in the C-terminus. However, in silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000726306 SCV000343608 uncertain significance not provided 2016-08-01 criteria provided, single submitter clinical testing
Invitae RCV000636407 SCV000757846 uncertain significance Early infantile epileptic encephalopathy 2018-07-25 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1960 of the SCN8A protein (p.Arg1960Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs369346315, ExAC 0.003%). This variant has not been reported in the literature in individuals with SCN8A-related disease. ClinVar contains an entry for this variant (Variation ID: 207136). 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: "Deleterious"; 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.
Ambry Genetics RCV000719806 SCV000850676 uncertain significance History of neurodevelopmental disorder 2017-05-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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.