Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002313381 | SCV000739146 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2016-07-01 | criteria provided, single submitter | clinical testing | The p.V62I variant (also known as c.184G>A), located in coding exon 2 of the MED12 gene, results from a G to A substitution at nucleotide position 184. The valine at codon 62 is replaced by isoleucine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6047 samples with coverage at this position. This amino acid position is well conserved in available vertebrate species; however, isoleucine is the reference amino acid in other 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 | RCV003762837 | SCV003456266 | uncertain significance | FG syndrome | 2022-05-20 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 519902). This variant has not been reported in the literature in individuals affected with MED12-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 62 of the MED12 protein (p.Val62Ile). 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) performed at Invitae indicates that this missense variant is not expected to disrupt MED12 protein function. 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. |
| Laboratorio de Genetica e Diagnostico Molecular, |
RCV003139947 | SCV003807801 | uncertain significance | Cholestasis-pigmentary retinopathy-cleft palate syndrome | 2022-09-02 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PM2 moderated, PP2 supporting, BP4 supporting |