Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000520619 | SCV000618747 | likely pathogenic | not provided | 2017-07-06 | criteria provided, single submitter | clinical testing | The c.1662_1667delAGACAA variant in the MARS gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The c.1662_1667delAGACAA variant results in an in-frame deletion of two amino acid residues, starting with codon Lysine 554, denoted p.Lys554_Asp555del. This deletions contains residues that are conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. The c.1662_1667delAGACAA variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.1662_1667delAGACAA as a likely pathogenic variant. |
Invitae | RCV002527606 | SCV003277428 | uncertain significance | Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency; Charcot-Marie-Tooth disease axonal type 2U | 2023-04-28 | 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: 450196). This variant has not been reported in the literature in individuals affected with MARS-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.1662_1667del, results in the deletion of 2 amino acid(s) of the MARS protein (p.Lys554_Asp555del), but otherwise preserves the integrity of the reading frame. |
Genome |
RCV000709861 | SCV000840194 | not provided | MARS-Related Disorder | no assertion provided | phenotyping only | GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. |