Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000549972 | SCV000655650 | uncertain significance | Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency; Charcot-Marie-Tooth disease axonal type 2U | 2023-05-15 | 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. This variant has not been reported in the literature in individuals affected with MARS-related conditions. Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This sequence change creates a premature translational stop signal (p.Gln302Hisfs*8) in the MARS gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in MARS cause disease. |
| Ambry Genetics | RCV002461352 | SCV002755176 | pathogenic | Inborn genetic diseases | 2021-07-23 | criteria provided, single submitter | clinical testing | The c.906_919del14insCTC pathogenic mutation, located in coding exon 9 of the MARS gene, results from the deletion of 14 nucleotides and insertion of 3 nucleotides causing a translational frameshift with a predicted alternate stop codon (p.Q302Hfs*8). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Although biallelic loss of function alterations in MARS have been associated with interstitial lung and liver disease, haploinsufficiency for MARS has not been clearly established as a mechanism of disease for axonal Charcot-Marie-Tooth disease, type 2U (CMT2U). Based on the supporting evidence, this variant is expected to be causative of interstitial lung and liver disease when present along with a second pathogenic variant on the other allele; however, its clinical significance for CMT2U is unclear. |