ClinVar Miner

Submissions for variant NM_018127.7(ELAC2):c.2245C>T (p.His749Tyr)

gnomAD frequency: 0.00007  dbSNP: rs762471494
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001063998 SCV001228870 uncertain significance Combined oxidative phosphorylation defect type 17 2022-05-12 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 749 of the ELAC2 protein (p.His749Tyr). This variant is present in population databases (rs762471494, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of ELAC2-related conditions (PMID: 31045291). ClinVar contains an entry for this variant (Variation ID: 858177). 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"). 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.
Fulgent Genetics, Fulgent Genetics RCV002482078 SCV002791451 uncertain significance Prostate cancer, hereditary, 2; Combined oxidative phosphorylation defect type 17 2021-07-09 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003425905 SCV004118125 likely pathogenic ELAC2-related disorder 2023-07-12 criteria provided, single submitter clinical testing The ELAC2 c.2245C>T variant is predicted to result in the amino acid substitution p.His749Tyr. This variant was reported in the compound heterozygous state along with a loss-of-function variant in two individuals with hypertrophic cardiomyopathy or suspected mitochondrial disorders (Patient #P12, Saoura et al. 2019. PubMed ID: 31045291; Schon et al. 2021. PubMed ID: 34732400). In vitro functional studies showed that this variant results in altered protein function and RNA samples from the affected patient showed increased amounts of 3′ end unprocessed mt-tRNA precursors at multiple cleavage sites (Table 3 and Figure S2, Saoura et al. 2019. PubMed ID: 31045291). This variant is reported in 0.016% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-12897012-G-A). This variant is interpreted as likely pathogenic.

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