Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV000756320 | SCV000884091 | uncertain significance | not provided | 2018-01-22 | criteria provided, single submitter | clinical testing | The MARS c.228G>T; p.Glu76Asp variant (rs369313141), to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the genome Aggregation Database (gnomAD) with an overall population frequency of 0.002% (identified on 5 out of 246,264 chromosomes). The glutamic acid at position 76 is moderately conserved, considering 12 species, and computational analyses of the effects of the p.Glu76Asp variant on protein structure and function do not predict a deleterious effect (SIFT: tolerated, MutationTaster: polymorphism, PolyPhen-2: benign). Based on the available information, the clinical significance of the p.Glu76Asp variant cannot be determined with certainty. |
Invitae | RCV001069411 | SCV001234575 | uncertain significance | Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency; Charcot-Marie-Tooth disease axonal type 2U | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 76 of the MARS protein (p.Glu76Asp). This variant is present in population databases (rs369313141, gnomAD 0.007%). 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: 618205). 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 tolerated. 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. |