Submissions for variant NM_004519.4(KCNQ3):c.2443G>T (p.Asp815Tyr) (rs530506549)

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	RCV000188000	SCV000241603	uncertain significance	not provided	2012-08-31	criteria provided, single submitter	clinical testing	p.Asp815Tyr (GAT>TAT):c.2443 G>T in exon 15 of the KCNQ3 gene (NM_004519.2) The Asp815Tyr 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 Asp815Tyr in approximately 6,500 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. This amino acid substitution is non-conservative, as a negatively charged Aspartic acid residue is replaced by a uncharged Tyrosine residue. Asp815Tyr alters a conserved position in the C-terminal region of the protein, and multiple in silico algorithms predict it is damaging to the structure and/or function of the KCNQ3 protein. However, to our knowledge other missense mutations have not been previously reported near Asp815Tyr. Therefore, based on the currently available information, it is unclear whether Asp815Tyr is a disease-causing mutation or a rare benign variant. The variant is found in INFANT-EPI panel(s).
Invitae	RCV000647887	SCV000769691	uncertain significance	Benign familial neonatal seizures	2018-11-29	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid with tyrosine at codon 815 of the KCNQ3 protein (p.Asp815Tyr). The aspartic acid residue is moderately conserved and there is a large physicochemical difference between aspartic acid and tyrosine. This variant is present in population databases (rs530506549, ExAC 0.03%). This variant has not been reported in the literature in individuals with KCNQ3-related disease. ClinVar contains an entry for this variant (Variation ID: 205994). 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: "Probably Damaging"; Align-GVGD: "Class C15"). 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.