ClinVar Miner

Submissions for variant NM_004519.4(KCNQ3):c.2614A>G (p.Ile872Val) (rs199682667)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188001 SCV000241604 uncertain significance not provided 2017-03-16 criteria provided, single submitter clinical testing p.Ile872Val (I872V): c.2614 A>G. The I872V variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The I872V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, this substitution occurs at a position that is not conserved across species, and Valine has been seen at this position in multiple species in evolution. In silico analysis predicts this variant likely does not alter the protein structure/function. However, the I872V variant was not observed with any significant frequency 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 I872V may be a benign variant, however, the possibility that it is a disease-associated mutation cannot be excluded.The variant is found in EPILEPSY panel(s).
Fulgent Genetics,Fulgent Genetics RCV000765987 SCV000897419 uncertain significance Benign familial neonatal seizures 2 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000799369 SCV000939028 uncertain significance Benign familial neonatal seizures 2018-11-05 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 872 of the KCNQ3 protein (p.Ile872Val). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs199682667, ExAC 0.006%). This variant has not been reported in the literature in individuals with KCNQ3-related disease. ClinVar contains an entry for this variant (Variation ID: 205995). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.

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