ClinVar Miner

Submissions for variant NM_004700.4(KCNQ4):c.1531G>A (p.Val511Ile)

gnomAD frequency: 0.00001  dbSNP: rs778538229
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000219909 SCV000271882 uncertain significance not specified 2016-01-15 criteria provided, single submitter clinical testing The p.Val511Ile variant in KCNQ4 has not been previously reported in individuals with hearing loss, but has been identified in 1/16510 South Asian chromosomes b y the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs778538229). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational predi ction tools and conservation analyses suggest that the p.Val511Ile variant may n ot impact the protein, though this information is not predictive enough to rule out pathogenicity. Of note, one mammal (Cape elephant shrew) has an isoleucine ( Ile) at this position despite nearby amino acid conservation. In summary, the cl inical significance of the p.Val511Ile variant is uncertain.
Invitae RCV002519633 SCV003272178 uncertain significance not provided 2023-08-28 criteria provided, single submitter clinical testing 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. 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 not expected to disrupt KCNQ4 protein function. ClinVar contains an entry for this variant (Variation ID: 228770). This variant has not been reported in the literature in individuals affected with KCNQ4-related conditions. This variant is present in population databases (rs778538229, gnomAD 0.003%). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 511 of the KCNQ4 protein (p.Val511Ile).
Genome-Nilou Lab RCV003445712 SCV004173820 uncertain significance Autosomal dominant nonsyndromic hearing loss 2A 2023-04-11 criteria provided, single submitter clinical testing

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