ClinVar Miner

Submissions for variant NM_007254.4(PNKP):c.1360C>G (p.Leu454Val)

dbSNP: rs200611702
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000809805 SCV000949981 uncertain significance Developmental and epileptic encephalopathy, 12 2022-08-23 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 missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 653942). This variant has not been reported in the literature in individuals affected with PNKP-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.02%). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 454 of the PNKP protein (p.Leu454Val).
Knight Diagnostic Laboratories, Oregon Health and Sciences University RCV001270054 SCV001448789 uncertain significance Microcephaly, seizures, and developmental delay 2019-07-08 criteria provided, single submitter clinical testing
GeneDx RCV001759560 SCV001995156 uncertain significance not provided 2019-10-30 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002537319 SCV003734289 uncertain significance Inborn genetic diseases 2022-02-11 criteria provided, single submitter clinical testing The c.1360C>G (p.L454V) alteration is located in exon 15 (coding exon 14) of the PNKP gene. This alteration results from a C to G substitution at nucleotide position 1360, causing the leucine (L) at amino acid position 454 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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