Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000197721 | SCV000250597 | uncertain significance | not provided | 2016-12-19 | criteria provided, single submitter | clinical testing | p.Ile2047Val (ATC>GTC): c.6139 A>G in exon 42 in the MED12 gene (NM_005120.2) A variant of uncertain significance has been identified in the MED12 gene. The I2047V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, the I2047V variant has been reported in 0.1% alleles from individuals of East Asian ancestry, including three hemizygous individuals, in the Exome Aggregation Consortium. The I2047V 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 where amino acids with similar properties to Isoleucine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Nevertheless, the phenotypic and pathogenic variant spectrum of MED12-related disorders is not well established in females and correlation with the clinical features in this individual is recommended. |
| Invitae | RCV003761819 | SCV002410181 | benign | FG syndrome | 2023-08-07 | criteria provided, single submitter | clinical testing |