ClinVar Miner

Submissions for variant NM_018100.4(EFHC1):c.1370G>T (p.Arg457Leu)

gnomAD frequency: 0.00010  dbSNP: rs369468811
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187361 SCV000240946 uncertain significance not provided 2015-10-06 criteria provided, single submitter clinical testing The R457L variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The R457L variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The R457L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense mutations in nearby residues have not been reported. The variant is found in EPILEPSY panel(s).
Illumina Laboratory Services, Illumina RCV000295753 SCV000464171 uncertain significance Juvenile myoclonic epilepsy 2016-06-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV003765184 SCV000941372 uncertain significance Absence seizure; Myoclonic epilepsy, juvenile, susceptibility to, 1 2022-07-11 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with EFHC1-related conditions. This variant is present in population databases (rs369468811, gnomAD 0.04%). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 457 of the EFHC1 protein (p.Arg457Leu). This missense change has been observed in at least one individual who was not affected with EFHC1-related conditions (Invitae). 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: "Probably Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 205404).

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