ClinVar Miner

Submissions for variant NM_007254.4(PNKP):c.1255G>A (p.Val419Ile)

gnomAD frequency: 0.00001  dbSNP: rs756416098
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188451 SCV000242065 uncertain significance not provided 2021-04-20 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV000576212 SCV000677005 uncertain significance Developmental and epileptic encephalopathy, 12 2024-12-09 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 419 of the PNKP protein (p.Val419Ile). This variant is present in population databases (rs756416098, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with PNKP-related conditions. ClinVar contains an entry for this variant (Variation ID: 206407). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt PNKP protein function with a negative predictive value of 80%. 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 RCV002415812 SCV002681162 uncertain significance Inborn genetic diseases 2019-11-15 criteria provided, single submitter clinical testing The p.V419I variant (also known as c.1255G>A), located in coding exon 13 of the PNKP gene, results from a G to A substitution at nucleotide position 1255. The valine at codon 419 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is well conserved in available 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.
Breakthrough Genomics, Breakthrough Genomics RCV000188451 SCV005194760 uncertain significance not provided criteria provided, single submitter not provided

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