ClinVar Miner

Submissions for variant NM_018100.4(EFHC1):c.266A>G (p.His89Arg)

gnomAD frequency: 0.00008  dbSNP: rs543160745
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187379 SCV000240964 uncertain significance not provided 2013-04-25 criteria provided, single submitter clinical testing This variant is denoted as NM_018100.3:c.266A>G; p.H89R:CAT>CGT. This missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The amino acid substitution is conservative as both Histidine and Arginine are positively charged amino acid residues and His89Arg alters a position that is not well conserved in the protein. However, in-silico models are not consistent in their predictions of whether His89Arg is damaging to the structure/function of the protein. The variant is found in EPILEPSY panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV003765190 SCV000552790 uncertain significance Absence seizure; Myoclonic epilepsy, juvenile, susceptibility to, 1 2020-06-22 criteria provided, single submitter clinical testing This sequence change replaces histidine with arginine at codon 89 of the EFHC1 protein (p.His89Arg). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and arginine. 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 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"). This variant has been observed in individual(s) with juvenile myoclonic epilepsy (PMID: 28370826, 27467453). This variant is present in population databases (rs543160745, ExAC 0.08%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811).

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