ClinVar Miner

Submissions for variant NM_004974.4(KCNA2):c.68A>G (p.Tyr23Cys)

gnomAD frequency: 0.00002  dbSNP: rs753829876
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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 RCV000558487 SCV000656458 uncertain significance Developmental and epileptic encephalopathy, 32 2024-06-22 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 23 of the KCNA2 protein (p.Tyr23Cys). This variant is present in population databases (rs753829876, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of KCNA2-related conditions (Invitae). In at least one individual the variant was observed to be de novo. This missense change has been observed in at least one individual who was not affected with KCNA2-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 476053). 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 KCNA2 protein function with a negative predictive value of 95%. 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 RCV002367957 SCV002662961 uncertain significance Inborn genetic diseases 2019-12-13 criteria provided, single submitter clinical testing The p.Y23C variant (also known as c.68A>G), located in coding exon 1 of the KCNA2 gene, results from an A to G substitution at nucleotide position 68. The tyrosine at codon 23 is replaced by cysteine, an amino acid with highly dissimilar 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 limited at this time, the clinical significance of this alteration remains unclear.

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