ClinVar Miner

Submissions for variant NM_004982.4(KCNJ8):c.760A>G (p.Ile254Val)

dbSNP: rs1235054283
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002006660 SCV002293151 uncertain significance Brugada syndrome 2021-11-08 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 KCNJ8 protein function. This variant has not been reported in the literature in individuals affected with KCNJ8-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 254 of the KCNJ8 protein (p.Ile254Val).
Ambry Genetics RCV002389024 SCV002671841 uncertain significance Cardiovascular phenotype 2022-06-07 criteria provided, single submitter clinical testing The p.I254V variant (also known as c.760A>G), located in coding exon 2 of the KCNJ8 gene, results from an A to G substitution at nucleotide position 760. The isoleucine at codon 254 is replaced by valine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and valine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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