ClinVar Miner

Submissions for variant NM_004519.4(KCNQ3):c.1043C>T (p.Ala348Val)

dbSNP: rs796052679
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187972 SCV000241575 uncertain significance not provided 2013-07-29 criteria provided, single submitter clinical testing p.Ala348Val (GCG>GTG): c.1043 C>T in exon 6 of the KCNQ3 gene (NM_004519.2) The Ala348Val 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 6,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Ala348Val alters a conserved position in the sixth transmembrane domain of the KCNQ3 protein and another missense mutation in this region of the protein has been reported in association with benign familial neonatal seizures (Li et al., 2008). In addition, in silico analysis predicts this variant is probably damaging to the protein structure/function. However, the amino acid substitution is conservative as both Alanine and Valine are uncharged, non-polar amino acid residues. Therefore, based on the currently available information, it is unclear whether Ala348Val is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV001347573 SCV001541841 uncertain significance Benign neonatal seizures 2023-10-03 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 348 of the KCNQ3 protein (p.Ala348Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of KCNQ3-related conditions (PMID: 32613771). ClinVar contains an entry for this variant (Variation ID: 205967). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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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