Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000472803 | SCV000550941 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2022-03-19 | 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. 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"). ClinVar contains an entry for this variant (Variation ID: 410313). This variant has not been reported in the literature in individuals affected with GARS-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 66 of the GARS protein (p.Pro66Ser). |
| Ambry Genetics | RCV004022756 | SCV002755205 | uncertain significance | not specified | 2020-12-02 | criteria provided, single submitter | clinical testing | The p.P66S variant (also known as c.196C>T), located in coding exon 1 of the GARS gene, results from a C to T substitution at nucleotide position 196. The proline at codon 66 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |