ClinVar Miner

Submissions for variant NM_004700.4(KCNQ4):c.1342C>T (p.Arg448Trp)

gnomAD frequency: 0.00005  dbSNP: rs535365858
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002251660 SCV002522073 uncertain significance not provided 2021-11-29 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV002251660 SCV003444169 uncertain significance not provided 2022-11-08 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on KCNQ4 protein function. ClinVar contains an entry for this variant (Variation ID: 1687686). This variant has not been reported in the literature in individuals affected with KCNQ4-related conditions. This variant is present in population databases (rs535365858, gnomAD 0.009%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 448 of the KCNQ4 protein (p.Arg448Trp).
Ambry Genetics RCV003094098 SCV003722209 uncertain significance Inborn genetic diseases 2022-11-07 criteria provided, single submitter clinical testing The c.1342C>T (p.R448W) alteration is located in exon 10 (coding exon 10) of the KCNQ4 gene. This alteration results from a C to T substitution at nucleotide position 1342, causing the arginine (R) at amino acid position 448 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV003445155 SCV004173753 uncertain significance Autosomal dominant nonsyndromic hearing loss 2A 2023-04-11 criteria provided, single submitter clinical testing

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