ClinVar Miner

Submissions for variant NM_005120.3(MED12):c.3067A>G (p.Ile1023Val)

dbSNP: rs879255526
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV003595900 SCV002179909 uncertain significance FG syndrome 2022-07-05 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: 252963). This missense change has been observed in individual(s) with intellectual disability and dysmorphic facial features (PMID: 27081531, 32779332). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1023 of the MED12 protein (p.Ile1023Val).
Revvity Omics, Revvity RCV003133195 SCV003810873 uncertain significance not provided 2022-03-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV003165677 SCV003869402 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-01-08 criteria provided, single submitter clinical testing The p.I1023V variant (also known as c.3067A>G), located in coding exon 22 of the MED12 gene, results from an A to G substitution at nucleotide position 3067. The isoleucine at codon 1023 is replaced by valine, an amino acid with highly similar properties. This variant has been detected in a hemizygous male reported to have non-specific X-linked intellectual disability with some dysmorphic features (Yamamoto T et al. Hum Genome Var, 2015 Jun;2:15018). This amino acid position is not 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 alteration remains unclear.
GeneReviews RCV000239400 SCV000297768 not provided FG syndrome 1 no assertion provided literature only Reported in a male with nonspecific intellectual disability

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