ClinVar Miner

Submissions for variant NM_005120.3(MED12):c.5898dup (p.Ser1967fs) (rs879255527)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001008098 SCV001167844 likely pathogenic not provided 2018-11-05 criteria provided, single submitter clinical testing The c.5898dupC variant in the MED12 gene has been reported previously in a family with intellectual disability and dysmorphic features and it is associated with mild to severe symptoms in both males and females (Lesca et al., 2013). The duplication causes a frameshift starting with codon Serine 1967, changes this amino acid to a Glutamine residue and creates a premature Stop codon at position 84 of the new reading frame, denoted p.Ser1967GlnfsX84. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. However, RNA expression studies show that the mutated allele was not degraded by nonsense-mediated RNA decay and induced an additional abnormal isoform due to activation of cryptic splice sites (Lesca et al., 2013). The c.5898dupC variant is not observed in large population cohorts (Lek et al., 2016). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
GeneReviews RCV000239399 SCV000297773 pathogenic FG syndrome 1 2016-08-11 no assertion criteria provided literature only

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