ClinVar Miner

Submissions for variant NM_001151.4(SLC25A4):c.239G>A (p.Arg80His)

dbSNP: rs886041081
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000479591 SCV000565573 pathogenic not provided 2022-12-22 criteria provided, single submitter clinical testing Published functional studies suggest a damaging effect, as structural analysis suggests R80H affects the proposed substrate-binding site, and in-vitro assays detected a reduced ADP transport rate in the R80H mutant construct as compared to wild type (Thompson et al., 2016); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27693233, 30009132, 31271879, 32827528)
Ambry Genetics RCV000624243 SCV000740715 pathogenic Inborn genetic diseases 2016-09-29 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000258873 SCV004022280 pathogenic Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type), autosomal dominant 2023-07-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000479591 SCV004292776 pathogenic not provided 2023-10-06 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 80 of the SLC25A4 protein (p.Arg80His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant SLC25A4-related conditions (PMID: 27693233, 32827528). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 253037). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SLC25A4 protein function. Experimental studies have shown that this missense change affects SLC25A4 function (PMID: 27693233). For these reasons, this variant has been classified as Pathogenic.
Wellcome Centre for Mitochondrial Research, Newcastle University RCV000491010 SCV000297809 pathogenic Mitochondrial disease 2016-08-06 no assertion criteria provided clinical testing
OMIM RCV000258873 SCV000328650 pathogenic Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type), autosomal dominant 2016-11-14 no assertion criteria provided literature only

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