Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002313968 | SCV000739139 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2016-02-04 | criteria provided, single submitter | clinical testing | The p.Q1974H variant (also known as c.5922G>T), located in coding exon 41 of the MED12 gene, results from a G to T substitution at nucleotide position 5922. The glutamine at codon 1974 is replaced by histidine, an amino acid with highly similar properties. In a family study, this variant was observed to co-segregate with another alteration in the OGT gene in three brothers with severe non-syndromic intellectual deficiency and mild dysmorphic features (Bouazzi H et al. Clin Case Rep. 2015;3(7):604-9). In the same study, this variant, but not the OGT alteration, was confirmed in their mother who was described to have language delays and no dysmorphic features. 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 6230 samples with coverage at this position. This amino acid position is well conserved in available 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 variant remains unclear. |
Ce |
RCV000762650 | SCV000892984 | uncertain significance | not provided | 2018-07-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003595901 | SCV002184183 | uncertain significance | FG syndrome | 2021-08-11 | 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: 252965). This missense change has been observed in individual(s) with non-syndromic intellectual disability (PMID: 26273451). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with histidine at codon 1974 of the MED12 protein (p.Gln1974His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine. |
Gene |
RCV000239403 | SCV000297774 | not provided | FG syndrome 1 | no assertion provided | literature only | Reported in male sibs with nonspecific intellectual disability | |
Center for Medical Genetics and Molecular Medicine, |
RCV000515779 | SCV000611864 | benign | Intellectual disability | 2017-12-06 | no assertion criteria provided | clinical testing | Variant inherited from healthy grandfather of index patient |