ClinVar

Description

p.Met2033Val (M2033V) ATG>GTG: c.6097 A>G in exon 42 of the MED12 gene (NM_005120.2) The M2033V variant of unknown significance in the MED12 gene has not been published as a mutation or as a benign polymorphism to our knowledge. The 1000 Genomes Project reports M2033V was observed in 1/976 alleles (0.1%) from individuals of South Asian ancestry, indicating it may be a rare benign variant in this population. In silico analysis predicts this variant to be benign to protein structure/function. This residue is not conserved across species. However, the M2033V variant is predicted by in silico algorithms to create a cryptic splice donor site upstream of the natural splice donor site in intron 42, which may lead to abnormal gene splicing. However, in the absence of functional mRNA studies, the physiological consequence of this variant cannot be precisely determined. No missense mutations in nearby residues and no splice mutations have been reported in association with disease, indicating this region of the protein may be tolerant of change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. This variant was found in TAADV2-PANCARD