Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000652565 | SCV000774435 | uncertain significance | Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency; Charcot-Marie-Tooth disease axonal type 2U | 2023-05-18 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with MARS-related conditions. 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. 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. ClinVar contains an entry for this variant (Variation ID: 542177). This variant is present in population databases (rs769544594, gnomAD 0.08%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 394 of the MARS protein (p.Arg394His). |
| Ambry Genetics | RCV003352975 | SCV004073566 | uncertain significance | Inborn genetic diseases | 2023-06-16 | criteria provided, single submitter | clinical testing | The c.1181G>A (p.R394H) alteration is located in exon 10 (coding exon 10) of the MARS1 gene. This alteration results from a G to A substitution at nucleotide position 1181, causing the arginine (R) at amino acid position 394 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |