ClinVar Miner

Submissions for variant NM_007254.4(PNKP):c.539G>A (p.Arg180His)

dbSNP: rs779492301
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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 RCV000477175 SCV000549902 uncertain significance Developmental and epileptic encephalopathy, 12 2021-08-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 180 of the PNKP protein (p.Arg180His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs779492301, ExAC 0.009%). This variant has not been reported in the literature in individuals affected with PNKP-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 RCV004022729 SCV005008269 uncertain significance Inborn genetic diseases 2023-11-21 criteria provided, single submitter clinical testing The c.539G>A (p.R180H) alteration is located in exon 5 (coding exon 4) of the PNKP gene. This alteration results from a G to A substitution at nucleotide position 539, causing the arginine (R) at amino acid position 180 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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