ClinVar Miner

Submissions for variant NM_005120.3(MED12):c.1561C>T (p.Arg521Cys)

dbSNP: rs1602295979
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV004702549 SCV005201317 uncertain significance not provided 2024-01-29 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; Reported in an abstract in a patient with features of MED12-related neurodevelopmental and multiple anomalies spectrum disorder (Weaver N et al. https://doi.org/10.1016/j.gimo.2023.100378); This variant is associated with the following publications: (PMID: 26813965, 33035779, Weaver2023[casereport])
Labcorp Genetics (formerly Invitae), Labcorp RCV005092961 SCV005733118 uncertain significance FG syndrome 2025-01-27 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 521 of the MED12 protein (p.Arg521Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MED12-related conditions. ClinVar contains an entry for this variant (Variation ID: 800764). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt MED12 protein function with a positive predictive value of 95%. 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.
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City RCV000984932 SCV001132845 uncertain significance X-linked MED12-related disorder 2019-01-29 no assertion criteria provided clinical testing

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