ClinVar Miner

Submissions for variant NM_005120.3(MED12):c.1849A>G (p.Thr617Ala) (rs765417606)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000224083 SCV000250602 uncertain significance not provided 2015-11-20 criteria provided, single submitter clinical testing p.Thr617Ala (ACT>GCT): c.1849 A>G in exon 13 of the MED12 gene (NM_005120.2) The T617A variant of unknown significant in the MED12 gene has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The T617A variant was not observed in approximately 6,100 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 T617A variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to protein structure/function. However, no missense mutations in nearby residues have been reported in association with LS or related disorders indicating that this region of the protein may be tolerant of change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. This variant was found in TAAD
UCLA Clinical Genomics Center, UCLA RCV000199251 SCV000255409 likely pathogenic X-linked mental retardation with marfanoid habitus syndrome; FG syndrome 1; Ohdo syndrome, X-linked 2013-04-23 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224083 SCV000281467 uncertain significance not provided 2016-04-29 criteria provided, single submitter clinical testing Converted during submission to Uncertain significance.
Ambry Genetics RCV000622207 SCV000739138 uncertain significance Cardiovascular phenotype 2018-08-09 criteria provided, single submitter clinical testing The p.T617A variant (also known as c.1849A>G), located in coding exon 13 of the MED12 gene, results from an A to G substitution at nucleotide position 1849. The threonine at codon 617 is replaced by alanine, an amino acid with similar properties. This alteration was identified in an individual with autism, craniofacial dysmorphic features, and it was inherited from his mother (Lee H et al. JAMA, 2014 Nov;312:1880-7). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis.

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