ClinVar Miner

Submissions for variant NM_007254.4(PNKP):c.625G>A (p.Glu209Lys)

gnomAD frequency: 0.00001  dbSNP: rs773641701
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000179469 SCV000231723 uncertain significance not provided 2014-05-22 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000232964 SCV000289723 uncertain significance Developmental and epileptic encephalopathy, 12 2024-12-09 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 209 of the PNKP protein (p.Glu209Lys). This variant is present in population databases (rs773641701, gnomAD 0.03%). 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: 198198). 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.
Fulgent Genetics, Fulgent Genetics RCV002485174 SCV002777788 uncertain significance Charcot-Marie-Tooth disease type 2B2; Microcephaly, seizures, and developmental delay; Ataxia - oculomotor apraxia type 4 2022-03-28 criteria provided, single submitter clinical testing
Ambry Genetics RCV002516792 SCV003689282 uncertain significance Inborn genetic diseases 2022-11-21 criteria provided, single submitter clinical testing The c.625G>A (p.E209K) alteration is located in exon 6 (coding exon 5) of the PNKP gene. This alteration results from a G to A substitution at nucleotide position 625, causing the glutamic acid (E) at amino acid position 209 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.