ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.3190G>T (p.Asp1064Tyr) (rs769395683)

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 RCV000189131 SCV000242763 uncertain significance not provided 2015-05-12 criteria provided, single submitter clinical testing The Asp1064Tyr missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The NHLBI ESP Exome Variant Project has not identified Asp1064Tyr in approximately 6,500 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. The amino acid substitution is non-conservative as a negatively charged Aspartic acid residue is replaced by an uncharged Tyrosine residue. In addition, Asp1064Tyr alters a position that is conserved in mammals, and is within the intracellular loop between the second and third transmembrane domain of the SCN2A protein where other missense mutations have been published in association with neonatal-infantile seizures (Berkovic et al., 2004; Ogiwara et al., 2009). However, in-silico algorithms are not consistent in their predictions as to whether Asp1064Tyr is damaging to the structure/function of the protein. Therefore, based on the currently available information, it is unclear whether Asp1064Tyr is a disease-causing mutation or a rare benign variant. The variant is found in CHILD-EPI panel(s).
Invitae RCV000228684 SCV000290577 uncertain significance Benign familial neonatal-infantile seizures; Early infantile epileptic encephalopathy 11 2016-03-01 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with tyrosine at codon 1064 of the SCN2A protein (p.Asp1064Tyr). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and tyrosine. This variant is present in population databases (rs769395683, ExAC 0.02%) but has not been reported in the literature in individuals with a SCN2A-related disease. ClinVar contains an entry for this variant (Variation ID: 206982). This variant is within the intracellular loop between the second and third transmembrane domain of the SCN2A protein where other missense mutations have been published in association with severe myoclonic epilepsy of infancy and benign familial neonatal infantile seizures (PMID:22905747). 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 C15"). In summary, this variant is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Fulgent Genetics,Fulgent Genetics RCV000228684 SCV000895297 uncertain significance Benign familial neonatal-infantile seizures; Early infantile epileptic encephalopathy 11 2018-10-31 criteria provided, single submitter clinical testing

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.