Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001049683 | SCV001213749 | uncertain significance | Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency; Charcot-Marie-Tooth disease axonal type 2U | 2024-01-17 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 713 of the MARS protein (p.Arg713Gln). This variant is present in population databases (rs200011880, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 846387). 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. |
Ambry Genetics | RCV002462287 | SCV002755089 | likely benign | Inborn genetic diseases | 2019-08-28 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Prevention |
RCV003413848 | SCV004116102 | uncertain significance | MARS1-related condition | 2023-01-03 | criteria provided, single submitter | clinical testing | The MARS1 c.2138G>A variant is predicted to result in the amino acid substitution p.Arg713Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.021% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-57908775-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |