Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Genetics Laboratory, |
RCV001173441 | SCV001336530 | uncertain significance | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing | ||
Invitae | RCV002240746 | SCV002509618 | uncertain significance | Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency; Charcot-Marie-Tooth disease axonal type 2U | 2023-05-08 | criteria provided, single submitter | clinical testing | 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 917041). This variant has not been reported in the literature in individuals affected with MARS-related conditions. This variant is present in population databases (rs151196994, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 118 of the MARS protein (p.Arg118Trp). |
Ambry Genetics | RCV002462343 | SCV002755055 | uncertain significance | Inborn genetic diseases | 2019-11-21 | criteria provided, single submitter | clinical testing | The p.R118W variant (also known as c.352C>T), located in coding exon 4 of the MARS gene, results from a C to T substitution at nucleotide position 352. The arginine at codon 118 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is not well 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. |