Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000208685 | SCV005062141 | likely pathogenic | Mitochondrial DNA depletion syndrome 1 | 2024-03-21 | criteria provided, single submitter | clinical testing | Variant summary: TYMP c.518T>G (p.Met173Arg) results in a non-conservative amino acid change located in the Glycosyl transferase, family 3 domain (IPR000312) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. This variant alters the nucleotide within the exonic splice region in exon 5. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251330 control chromosomes. c.518T>G has been reported in the literature at a homozygous state in three Dominican individuals affected with Mitochondrial DNA Depletion Syndrome 1 (MNGIE type) (example, Garone_2011, Hirano_2004, Nishino_2000). 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: 21933806, 14720311, 10852545). ClinVar contains an entry for this variant (Variation ID: 223031). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Gene |
RCV004767153 | SCV005376458 | likely pathogenic | not provided | 2024-04-18 | criteria provided, single submitter | clinical testing | 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; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 10852545, 20301358, 21933806, 30627136, 19748572, 37448106) |
| Gene |
RCV000208685 | SCV000264513 | pathogenic | Mitochondrial DNA depletion syndrome 1 | 2016-01-14 | no assertion criteria provided | literature only |