ClinVar Miner

Submissions for variant NM_004519.4(KCNQ3):c.1226C>G (p.Pro409Arg)

gnomAD frequency: 0.00009  dbSNP: rs149272208
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000725748 SCV000241578 likely benign not provided 2019-12-03 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown; Has not been previously published as pathogenic or benign to our knowledge
Eurofins Ntd Llc (ga) RCV000725748 SCV000339132 uncertain significance not provided 2016-02-15 criteria provided, single submitter clinical testing
Invitae RCV000477245 SCV000543209 uncertain significance Benign neonatal seizures 2023-12-25 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 409 of the KCNQ3 protein (p.Pro409Arg). This variant is present in population databases (rs149272208, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with KCNQ3-related conditions. ClinVar contains an entry for this variant (Variation ID: 205970). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KCNQ3 protein function with a positive predictive value of 95%. 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.
Fulgent Genetics, Fulgent Genetics RCV000765990 SCV000897422 uncertain significance Seizures, benign familial neonatal, 2 2018-10-31 criteria provided, single submitter clinical testing

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