Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000652558 | SCV000774428 | uncertain significance | Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency; Charcot-Marie-Tooth disease axonal type 2U | 2023-01-12 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 542172). This variant has not been reported in the literature in individuals affected with MARS-related conditions. This variant is present in population databases (rs771808261, gnomAD 0.006%). This sequence change replaces proline, which is neutral and non-polar, with histidine, which is basic and polar, at codon 558 of the MARS protein (p.Pro558His). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. |
Molecular Genetics Laboratory, |
RCV001173444 | SCV001336533 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
Gene |
RCV001756101 | SCV001985270 | uncertain significance | not provided | 2019-08-15 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
Prevention |
RCV003420144 | SCV004117917 | uncertain significance | MARS1-related disorder | 2022-10-17 | criteria provided, single submitter | clinical testing | The MARS1 c.1673C>A variant is predicted to result in the amino acid substitution p.Pro558His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0054% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-57906056-C-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |