Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000479349 | SCV000574046 | likely pathogenic | not provided | 2018-09-20 | criteria provided, single submitter | clinical testing | The c.408+1G>A variant in the MPV17 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This splice site variant destroys the canonical splice donor site in intron 6. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.408+1G>A variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.408+1G>A as a likely pathogenic variant. |
| Fulgent Genetics, |
RCV000763082 | SCV000893606 | likely pathogenic | Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000479349 | SCV001576768 | likely pathogenic | not provided | 2024-01-29 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 6 of the MPV17 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MPV17 are known to be pathogenic (PMID: 23714749). This variant is present in population databases (rs749361266, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with MPV17-related conditions. ClinVar contains an entry for this variant (Variation ID: 424255). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Baylor Genetics | RCV004568213 | SCV005053362 | likely pathogenic | Charcot-Marie-Tooth disease, axonal, type 2EE | 2024-02-16 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV000763082 | SCV001462523 | likely pathogenic | Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) | 2020-09-16 | no assertion criteria provided | clinical testing |