Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001204493 | SCV001375702 | uncertain significance | Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency; Charcot-Marie-Tooth disease axonal type 2U | 2019-06-17 | criteria provided, single submitter | clinical testing | Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals with MARS-related conditions. This sequence change falls in intron 15 of the MARS gene. It does not directly change the encoded amino acid sequence of the MARS protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs183042263, ExAC 0.02%). |
| Ambry Genetics | RCV003353204 | SCV004077775 | uncertain significance | Inborn genetic diseases | 2023-07-18 | criteria provided, single submitter | clinical testing | Unlikely to be causative of MARS1-related Charcot-Marie-Tooth disease, type 2 (AD) Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |