Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001566923 | SCV001790513 | uncertain significance | not provided | 2020-09-29 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
| Labcorp Genetics |
RCV001566923 | SCV002297910 | uncertain significance | not provided | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 488 of the KCNQ4 protein (p.Arg488His). This variant is present in population databases (rs371301199, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with KCNQ4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1201537). 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. 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. |
| Ambry Genetics | RCV002570757 | SCV003702430 | uncertain significance | Inborn genetic diseases | 2022-12-28 | criteria provided, single submitter | clinical testing | The c.1463G>A (p.R488H) alteration is located in exon 10 (coding exon 10) of the KCNQ4 gene. This alteration results from a G to A substitution at nucleotide position 1463, causing the arginine (R) at amino acid position 488 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003331186 | SCV004039341 | uncertain significance | not specified | 2023-08-24 | criteria provided, single submitter | clinical testing | Variant summary: KCNQ4 c.1463G>A (p.Arg488His) results in a non-conservative amino acid change located in the Potassium channel, voltage dependent, KCNQ, C-terminal (IPR013821) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00012 in 236348 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1463G>A in individuals affected with Autosomal Dominant Nonsyndromic Hearing Loss 2A and no experimental evidence demonstrating its impact on protein function have been reported. Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Genome- |
RCV003446831 | SCV004173787 | uncertain significance | Autosomal dominant nonsyndromic hearing loss 2A | 2023-04-11 | criteria provided, single submitter | clinical testing |