Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000440933 | SCV000535927 | uncertain significance | not provided | 2017-01-06 | criteria provided, single submitter | clinical testing | The I285F variant in the MARS gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The I285F variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The I285F variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret I285F as a variant of uncertain significance. |
Invitae | RCV001218323 | SCV001390198 | uncertain significance | Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency; Charcot-Marie-Tooth disease axonal type 2U | 2023-12-09 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 285 of the MARS protein (p.Ile285Phe). This variant is present in population databases (rs776026574, gnomAD 0.004%). This missense change has been observed in individual(s) with clinical features of MARS-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 392628). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |