Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000197861 | SCV000250620 | uncertain significance | not provided | 2015-04-16 | criteria provided, single submitter | clinical testing | p.Ser698Asn (AGT>AAT): c.2093 G>A in exon 15 in the MED12 Gene (NM_005120.2). The S698N variant in the MED12 gene has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The S698N variant was not observed in approximately 6100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S698N variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret S698N as a variant of unknown significance. This variant was found in HG19-EXOME- |
Invitae | RCV003761825 | SCV001418049 | uncertain significance | FG syndrome | 2023-05-03 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 213647). 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 serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 698 of the MED12 protein (p.Ser698Asn). |