ClinVar Miner

Submissions for variant NM_004519.4(KCNQ3):c.856G>A (p.Val286Ile) (rs549372035)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187970 SCV000241573 uncertain significance not provided 2018-09-11 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the KCNQ3 gene. The V286I variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The V286I variant is observed in 8/30780 (0.03%) alleles from individuals of South Asian background in large population cohorts (Lek et al., 2016). The V286I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000647889 SCV000769693 uncertain significance Benign familial neonatal seizures 2018-03-08 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 286 of the KCNQ3 protein (p.Val286Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs549372035, 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: 205965). 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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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