ClinVar Miner

Submissions for variant NM_005120.3(MED12):c.1253G>A (p.Arg418His)

gnomAD frequency: 0.00001  dbSNP: rs1431487428
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002315454 SCV000849360 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2017-04-14 criteria provided, single submitter clinical testing The p.R418H variant (also known as c.1253G>A), located in coding exon 9 of the MED12 gene, results from a G to A substitution at nucleotide position 1253. The arginine at codon 418 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly 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 alteration remains unclear.
GeneDx RCV003128691 SCV003805331 uncertain significance not provided 2023-02-10 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV003768141 SCV004683200 uncertain significance FG syndrome 2023-05-19 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 expected to disrupt MED12 protein function. ClinVar contains an entry for this variant (Variation ID: 588961). 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 arginine, which is basic and polar, with histidine, which is basic and polar, at codon 418 of the MED12 protein (p.Arg418His).

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