Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000652556 | SCV000774426 | uncertain significance | Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency; Charcot-Marie-Tooth disease axonal type 2U | 2022-03-02 | criteria provided, single submitter | clinical testing | 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 542170). This variant has not been reported in the literature in individuals affected with MARS-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change creates a premature translational stop signal (p.Leu879Argfs*3) in the MARS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 22 amino acid(s) of the MARS protein. |
Prevention |
RCV003892489 | SCV004708880 | uncertain significance | MARS1-related condition | 2023-12-01 | criteria provided, single submitter | clinical testing | The MARS1 c.2631_2635dup5 variant is predicted to result in a frameshift and premature protein termination (p.Leu879Argfs*3). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0018% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Of note, not many loss of functions have been reported in the MARS1. In addition, this variant is present in the last exon of the gene and the impact on protein function in unknown. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |