Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000330566 | SCV000339504 | likely pathogenic | not provided | 2016-02-17 | criteria provided, single submitter | clinical testing | |
| Breakthrough Genomics, |
RCV004596155 | SCV005088826 | likely pathogenic | Mitochondrial DNA depletion syndrome 3 (hepatocerebral type) | 2020-04-11 | criteria provided, single submitter | clinical testing | This variant is predicted to be damaging by in-silico missense prediction tools (SIFT and Polyphen2). The variant was previously reported in a patient of Portugal origin diagnosed with mitochondrial DNA depletion syndrome and reported as pathogenic article [PMID: 19380071]. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004596155 | SCV005726903 | pathogenic | Mitochondrial DNA depletion syndrome 3 (hepatocerebral type) | 2024-11-08 | criteria provided, single submitter | clinical testing | Variant summary: DGUOK c.353G>A (p.Arg118His) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251438 control chromosomes. c.353G>A has been reported in the presumed compound heterozygous or homozygous state in the literature in multiple individuals affected with clinical features of Mitochondrial DNA depletion syndrome 3 (example, Canavati_2024, Dillon_2018, Diogo_2009, Dogulu_2021). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 38178268, 29453417, 19380071, 34167177). ClinVar contains an entry for this variant (Variation ID: 286174). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Prevention |
RCV003930119 | SCV004740844 | likely pathogenic | DGUOK-related disorder | 2023-10-23 | no assertion criteria provided | clinical testing | The DGUOK c.353G>A variant is predicted to result in the amino acid substitution p.Arg118His. This variant was reported in the heterozygous state with a second plausible causative variant in an individual with mitochondrial DNA depletion syndrome (Diogo et al. 2009. PubMed ID: 19380071). This variant was also reported in the homozygous state in two individuals with hepatic failure (Table S1, Dillon et al. 2018. PubMed ID: 29453417; Doğulu et al. 2021. PubMed ID: 34167177). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-74173943-G-A). Different nucleotide substitutions affecting the same amino acid (p.Arg118Cys and p.Arg118Leu) have been reported in individuals with mitochondrial DNA depletion syndrome (Dimmock et al. 2008. PubMed ID: 18205204; Haudry et al. 2012. PubMed ID: 23141463; Table S4, Yépez et al. 2022. PubMed ID: 35379322). Taken together, the c.353G>A (p.Arg118His) variant is interpreted as likely pathogenic. |