ClinVar Miner

Submissions for variant NM_004519.4(KCNQ3):c.2318G>A (p.Arg773Gln) (rs769160647)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187995 SCV000241598 uncertain significance not provided 2018-02-22 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the KCNQ3 gene. The R773Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is observed in 5/34414 (0.015%) alleles from individuals of Latino background in large population cohorts (Lek et al., 2016). TheR773Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, in-silico analyses, including protein predictors and evolutionaryconservation, support that this variant does not alter protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000792890 SCV000932216 uncertain significance Benign familial neonatal seizures 2018-08-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 773 of the KCNQ3 protein (p.Arg773Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs769160647, 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: 205989). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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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