ClinVar Miner

Submissions for variant NM_005120.3(MED12):c.1039A>G (p.Ser347Gly) (rs752300879)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000197655 SCV000250600 uncertain significance not provided 2016-07-19 criteria provided, single submitter clinical testing The S347G variant has not been published as a pathogenic or benign variant to our knowledge. This variant was not observed in approximately 6,300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant has been identified in conjunction with additional cardiogenetic variants in one individual referred for genetic testing for Marfan syndrome/TAAD at GeneDx; however, segregation data is limited or absent for this individual due to the lack of clinical information provided and/or insufficient participation by informative family members. The S347G 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. Nevertheless, this substitution occurs at a position that is not conserved, and G347 is tolerated in several species. Consequently, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Lastly, no missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with MED12-related disorders (Stenson et al., 2014).Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.
Ambry Genetics RCV000620563 SCV000739163 uncertain significance Cardiovascular phenotype 2017-05-09 criteria provided, single submitter clinical testing The p.S347G variant (also known as c.1039A>G), located in coding exon 7 of the MED12 gene, results from an A to G substitution at nucleotide position 1039. The serine at codon 347 is replaced by glycine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and glycine is the reference amino acid in other 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.
Fulgent Genetics,Fulgent Genetics RCV000766102 SCV000897581 uncertain significance X-linked mental retardation with marfanoid habitus syndrome; FG syndrome 1; Ohdo syndrome, X-linked 2018-10-31 criteria provided, single submitter clinical testing

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