Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Genetics Laboratory, |
RCV001173431 | SCV001336519 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
Ambry Genetics | RCV004032954 | SCV002755058 | uncertain significance | not specified | 2021-12-23 | criteria provided, single submitter | clinical testing | The p.T358S variant (also known as c.1073C>G), located in coding exon 9 of the MARS gene, results from a C to G substitution at nucleotide position 1073. The threonine at codon 358 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV002557488 | SCV003293853 | uncertain significance | Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency; Charcot-Marie-Tooth disease axonal type 2U | 2022-05-19 | criteria provided, single submitter | clinical testing | This missense change has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (PMID: 32376792). ClinVar contains an entry for this variant (Variation ID: 917034). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. This variant is present in population databases (rs746654999, gnomAD 0.003%). This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 358 of the MARS protein (p.Thr358Ser). |