Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001049989 | SCV001214074 | pathogenic | not provided | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 145 of the TYMP protein (p.Gly145Arg). This variant is present in population databases (rs121913037, gnomAD 0.007%). This missense change has been observed in individuals with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) (PMID: 9924029, 10852545, 16995425). It has also been observed to segregate with disease in related individuals. This variant is also known as G1419A. ClinVar contains an entry for this variant (Variation ID: 16655). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Revvity Omics, |
RCV000018135 | SCV002021572 | likely pathogenic | Mitochondrial DNA depletion syndrome 1 | 2021-02-03 | criteria provided, single submitter | clinical testing | |
MGZ Medical Genetics Center | RCV000018135 | SCV002578931 | likely pathogenic | Mitochondrial DNA depletion syndrome 1 | 2022-03-29 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001049989 | SCV002757027 | likely pathogenic | not provided | 2022-11-16 | 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: 19748572, 25525159, 9924029, 21820356, 16995425, 20301358, 18787099, 34288589) |
Fulgent Genetics, |
RCV000018135 | SCV002811634 | likely pathogenic | Mitochondrial DNA depletion syndrome 1 | 2021-12-30 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000018135 | SCV004029355 | pathogenic | Mitochondrial DNA depletion syndrome 1 | 2023-07-25 | criteria provided, single submitter | clinical testing | Variant summary: TYMP c.433G>A (p.Gly145Arg) results in a non-conservative amino acid change located in the Glycosyl transferase, family 3 (IPR000312) of 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 1.6e-05 in 250760 control chromosomes. c.433G>A has been reported in the literature in multiple individuals affected with Mitochondrial DNA Depletion Syndrome 1 (MNGIE type) (Example: Nishino_1999, Zaidman_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: 9924029, 33533561). Seven submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Baylor Genetics | RCV000018135 | SCV004207500 | pathogenic | Mitochondrial DNA depletion syndrome 1 | 2023-10-30 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000018135 | SCV000038414 | pathogenic | Mitochondrial DNA depletion syndrome 1 | 1999-01-29 | no assertion criteria provided | literature only | |
Gene |
RCV000018135 | SCV000264509 | pathogenic | Mitochondrial DNA depletion syndrome 1 | 2016-01-14 | no assertion criteria provided | literature only | |
Natera, |
RCV001276278 | SCV001462372 | likely pathogenic | Mitochondrial neurogastrointestinal encephalomyopathy | 2020-09-16 | no assertion criteria provided | clinical testing |