Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003597241 | SCV002161265 | uncertain significance | FG syndrome | 2023-05-23 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with MED12-related conditions. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MED12 protein function. ClinVar contains an entry for this variant (Variation ID: 1390351). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1536 of the MED12 protein (p.Arg1536Trp). |
| Ambry Genetics | RCV004039134 | SCV003651931 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2022-11-04 | criteria provided, single submitter | clinical testing | The c.4606C>T (p.R1536W) alteration is located in exon 33 (coding exon 33) of the MED12 gene. This alteration results from a C to T substitution at nucleotide position 4606, causing the arginine (R) at amino acid position 1536 to be replaced by a tryptophan (W). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. This missense alteration is located in a region that has a low rate of benign missense variation (Lek, 2016; Firth, 2009). This alteration is predicted to be deleterious by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |