ClinVar Miner

Submissions for variant NM_005120.3(MED12):c.6241_6243CAG[5] (p.Gln2086del) (rs786200971)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000198426 SCV000250623 uncertain significance not specified 2017-10-25 criteria provided, single submitter clinical testing The c.6256_6258delCAG variant in the MED12 gene has not been reported previously to our knowledge. This variant causes an in-frame deletion of a single amino acid, and does not shift the reading frame or create a premature stop codon. This variant occurs in a poly-glutamine tract in the glutamine-rich C-terminal region in the MED12 protein. This variant was not observed in approximately 6,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, other deletions of glutamine residues in this region have been observed at significant frequencies in this cohort, and have been identified in hemizygous males. No other in-frame deletions or insertions in the MED12 gene have been reported in association with disease. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.
Invitae RCV000544153 SCV000630360 uncertain significance FG syndrome 1 2018-02-06 criteria provided, single submitter clinical testing This sequence change deletes 3 nucleotides from exon 42 of the MED12 mRNA (c.6256_6258delCAG). This leads to the deletion of 1 amino acid residue in the MED12 protein (p.Gln2086del) but otherwise preserves the integrity of the reading frame. The frequency data for this variant (rs763466801) in the population databases is unreliable, as metrics indicate poor quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with a MED12-related disease. ClinVar contains an entry for this variant (Variation ID: 213650). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid is currently unknown. In summary, this variant is a rare in-frame deletion with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000622064 SCV000739132 likely benign Cardiovascular phenotype 2018-06-25 criteria provided, single submitter clinical testing Subpopulation frequency in support of benign classification;Other data supporting benign classification;Sub-population frequency in support of benign classification (not ava blue, manual h-w);Other strong data supporting benign classification
Ambry Genetics RCV000718240 SCV000849102 likely benign History of neurodevelopmental disorder 2017-12-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Subpopulation frequency in support of benign classification,Other data supporting benign classification,Sub-population frequency in support of benign classification (not ava blue, manual h-w),Other strong data supporting benign classification

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