Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000813502 | SCV000953864 | likely pathogenic | EAST syndrome | 2023-06-13 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 171 of the KCNJ10 protein (p.Arg171Gln). This variant is present in population databases (rs200320916, gnomAD 0.02%). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects KCNJ10 function (PMID: 32062759). 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 KCNJ10 protein function. ClinVar contains an entry for this variant (Variation ID: 656970). This missense change has been observed in individual(s) with KCNJ10-related condition (PMID: 32062759). It has also been observed to segregate with disease in related individuals. |
| Ambry Genetics | RCV002345850 | SCV002645610 | uncertain significance | Inborn genetic diseases | 2019-06-05 | criteria provided, single submitter | clinical testing | The p.R171Q variant (also known as c.512G>A), located in coding exon 1 of the KCNJ10 gene, results from a G to A substitution at nucleotide position 512. The arginine at codon 171 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV000813502 | SCV004100497 | likely pathogenic | EAST syndrome | criteria provided, single submitter | clinical testing | The missense variant p.R171Q in KCNJ10 (NM_002241.5) causes the same amino acid change as a previously established pathogenic variant. The p.R171Q variant is observed in 1/5,928 (0.0169%) alleles from individuals of Ashkenazi Jewish background in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The p.R171Q missense variant is predicted to be damaging by both SIFT and PolyPhen2. The arginine residue at codon 171 of KCNJ10 is conserved in all mammalian species. The nucleotide c.512 in KCNJ10 is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic. In the absence of another reportable variant the molecular diagnosis of KCNJ10-related disease is not confirmed |