Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001345104 | SCV001539203 | uncertain significance | EAST syndrome | 2022-02-03 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 181 of the KCNJ10 protein (p.Phe181Leu). This variant is present in population databases (rs374746230, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with KCNJ10-related conditions. ClinVar contains an entry for this variant (Variation ID: 1041315). 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 KCNJ10 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 | RCV002350634 | SCV002649356 | uncertain significance | Inborn genetic diseases | 2018-01-31 | criteria provided, single submitter | clinical testing | The p.F181L variant (also known as c.541T>C), located in coding exon 1 of the KCNJ10 gene, results from a T to C substitution at nucleotide position 541. The phenylalanine at codon 181 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is conflicting at this time, the clinical significance of this alteration remains unclear. |
Fulgent Genetics, |
RCV002493770 | SCV002783452 | uncertain significance | Autosomal recessive nonsyndromic hearing loss 4; Pendred syndrome; EAST syndrome | 2022-03-23 | criteria provided, single submitter | clinical testing |