ClinVar Miner

Submissions for variant NM_007254.4(PNKP):c.308C>T (p.Thr103Ile)

gnomAD frequency: 0.00033  dbSNP: rs115419706
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000723658 SCV000113439 uncertain significance not provided 2013-08-09 criteria provided, single submitter clinical testing
Invitae RCV000464512 SCV000549898 uncertain significance Developmental and epileptic encephalopathy, 12 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 103 of the PNKP protein (p.Thr103Ile). This variant is present in population databases (rs115419706, gnomAD 0.1%). 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: 95482). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
GeneDx RCV000723658 SCV000577235 uncertain significance not provided 2023-05-31 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 22508754)
Ambry Genetics RCV002316251 SCV000849820 uncertain significance Inborn genetic diseases 2019-02-17 criteria provided, single submitter clinical testing The p.T103I variant (also known as c.308C>T), located in coding exon 3 of the PNKP gene, results from a C to T substitution at nucleotide position 308. The threonine at codon 103 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is well conserved on limited sequence alignment; however, isoleucine 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.
Mayo Clinic Laboratories, Mayo Clinic RCV000723658 SCV001713024 uncertain significance not provided 2020-02-04 criteria provided, single submitter clinical testing

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