ClinVar Miner

Submissions for variant NM_018100.4(EFHC1):c.68C>T (p.Thr23Ile)

gnomAD frequency: 0.00001  dbSNP: rs779993809
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187351 SCV000240936 uncertain significance not provided 2014-02-04 criteria provided, single submitter clinical testing p.Thr23Ile (ACA>ATA): c.68 C>T in exon 2 of the EFHC1 gene (NM_018100.3). The Thr23Ile missense change in the EFHC1 gene 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. This variant is a non-conservative amino acid substitution of a polar Threonine residue with a non-polar Isoleucine residue. However, it alters a position that is not conserved across species, and Isoleucine is observed at this position in recent evolution in one other mammalian species. In silico analysis is inconsistent with regard to the effect this variant may have on the protein structure/function. Therefore, based on the currently available information, it is unclear whether Thr23Ile is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV003765178 SCV000831253 uncertain significance Absence seizure; Myoclonic epilepsy, juvenile, susceptibility to, 1 2022-07-25 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with EFHC1-related conditions. 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: "Benign"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 205394). This variant is present in population databases (rs779993809, gnomAD 0.002%). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 23 of the EFHC1 protein (p.Thr23Ile).

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