ClinVar Miner

Submissions for variant NM_018127.7(ELAC2):c.1532C>A (p.Ser511Tyr)

gnomAD frequency: 0.00001  dbSNP: rs1240684251
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Agnes Ginges Centre for Molecular Cardiology, Centenary Institute RCV001089603 SCV001245075 uncertain significance Primary dilated cardiomyopathy; Mitochondrial complex I deficiency 2018-03-02 criteria provided, single submitter research ELAC2 Ser511Tyr has not been previously reported and is absent from the Genome Aggregation Database (http://gnomad.broadinstitute.org/). We identified this variant in a proband with DCM and mitochondrial respiratory chain complex I deficiency. The proband also harboured a second variant (ELAC2 Gln523Ter). Both variants also segregate to the proband's sibling who was diagnosed with DCM. It is very probable that these variants in combinations are causing disease in a recessive manner, however there is not enough information to prove this. Based on the ACMG guidelines (Richards S, et al., 2015) this variant meets only the very rare in the general population criteria (PM2), therefore we classify ELAC2 Ser511Tyr as a variant of 'uncertain significance'.
Labcorp Genetics (formerly Invitae), Labcorp RCV001862661 SCV002162738 uncertain significance Combined oxidative phosphorylation defect type 17 2022-08-09 criteria provided, single submitter clinical testing 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 870074). This missense change has been observed in individual(s) with clinical features of combined oxidative phosphorylation deficiency (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 511 of the ELAC2 protein (p.Ser511Tyr).

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