ClinVar Miner

Submissions for variant NM_172107.4(KCNQ2):c.338C>T (p.Ser113Phe) (rs796052616)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187850 SCV000241450 likely pathogenic not provided 2013-06-20 criteria provided, single submitter clinical testing p.Ser113Phe (TCC>TTC): c.338 C>T in exon 2 of the KCNQ2 gene (NM_172107.2)The Ser113Phe missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It 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 amino acid substitution is non-conservative as a polar Serine residue is replaced by a non-polar Phenylalanine residue. Ser113Phe alters a conserved position in the KCNQ2 protein and another missense mutation at a nearby codon has been previously reported in association with epileptic encephalopathy ( Saitsu et al., 2012). In addition, several in-silico algorithms predict Ser113Phe may be damaging to the structure/function of the protein. Therefore, based on the currently available information, Ser113Phe is a strong candidate for a disease-causing mutation, although the possibility that it is a benign variant cannot be excluded. The variant is found in EPILEPSY panel(s).
Invitae RCV001070885 SCV001236163 uncertain significance Early infantile epileptic encephalopathy 2019-12-06 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 113 of the KCNQ2 protein (p.Ser113Phe). The serine residue is highly conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with epilepsy and/or neurodevelopmental disorders (PMID: 29655203). ClinVar contains an entry for this variant (Variation ID: 205862). 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: "Deleterious"; PolyPhen-2: "Possibly 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.

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