ClinVar

Description

This variant (rs200077222) affects the MT-TC gene which encodes the mitochondrial tRNA for cysteine, and has been described in the literature as both a pathogenic and benign variant. The m.5814T>C variant has historically been associated with MELAS-like syndromes, having been found in a heteroplasmic state in a Portuguese patient with episodic vomiting, lactic acidosis, seizures, hemiparesis and white matter abnormalities identified in a brain MRI (Manfredi 1996). It was also identified (heteroplasmic) in an Italian proband with hearing impairment, unsteady gait, hyporeflexia, nystagmus, and lactic acidosis (Santorelli 1997). However, the m.5814T>C variant was also identified in mildly effected and unaffected maternal relatives of the proband described in Santorelli (1997), and identified in a homoplasmic state in a different proband whose only clinical presentation was exercise intolerance and who also had several unaffected maternal relatives who carried the variant in a homoplasmic state (Sternberg 2001). Additionally, the m.5814T>C variant is found at 99% allele frequency in the L2b haplogroup which is primarily carried by individuals of African and Dominican descent (MITOMAP; trees described in Herrnstadt 2002 and Kivisild 2006), and is therefore present in presumably healthy individuals. Based on the available evidence, the m.5814T>C variant is unlikely to be a primary MELAS variant; however, a contributory role of this variant to MELAS expression cannot be excluded.