ClinVar Miner

Submissions for variant NM_018684.4(ZC4H2):c.638G>A (p.Arg213Gln)

dbSNP: rs2147345630
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV002255751 SCV002526540 likely pathogenic not provided 2022-03-23 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); 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
Labcorp Genetics (formerly Invitae), Labcorp RCV002255751 SCV004380867 uncertain significance not provided 2023-11-13 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 213 of the ZC4H2 protein (p.Arg213Gln). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ZC4H2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1691760). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Arg213 amino acid residue in ZC4H2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23623388, 26056227). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 RCV005301135 SCV005969420 uncertain significance Inborn genetic diseases 2024-12-11 criteria provided, single submitter clinical testing The c.638G>A (p.R213Q) alteration is located in exon 5 (coding exon 5) of the ZC4H2 gene. This alteration results from a G to A substitution at nucleotide position 638, causing the arginine (R) at amino acid position 213 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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