Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002726916 | SCV003002009 | uncertain significance | Charcot-Marie-Tooth disease type 2 | 2022-05-25 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 192 of the MED25 protein (p.Arg192Gln). 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 variant has not been reported in the literature in individuals affected with MED25-related conditions. 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: "Tolerated"; PolyPhen-2: "Probably 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. |
| ARUP Laboratories, |
RCV005233008 | SCV005878296 | uncertain significance | Congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome | 2024-07-25 | criteria provided, single submitter | clinical testing | The MED25 c.575G>A; p.Arg192Gln variant (rs753164820), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 1967670). This variant is only found on one allele in the Genome Aggregation Database (v2.1.1), indicating it is not a common polymorphism. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.286). Due to limited information, the clinical significance of this variant is uncertain at this time. |