The private pilot and three passengers departed on an instrument flight rules cross-country flight. About 2 hours into the flight, the pilot began to deviate around areas of precipitation and climbed the airplane from its previous cruise altitude of 10,000 ft mean sea level (msl) to 12,000 ft msl. Shortly thereafter, the air traffic controller told the pilot that moderate to extreme precipitation was ahead of the airplane and advised the pilot to deviate as necessary around it. Shortly thereafter, the airplane began a series of descending right turns. The controller advised the pilot to climb and maintain 12,000 ft several times; however, the airplane continued to turn and descend, and radar contact was lost at an altitude of about 2,000 ft msl. A witness reported hearing an airplane flying above, then heard a loud "boom" and saw pieces of the airplane falling from the sky. The wreckage path was about 4,550 ft in length, consistent with an in-flight breakup. Examination of the airframe and engine revealed no anomalies that would have precluded normal operation.The pilot received a weather briefing before departing on the accident flight that included a forecast for scattered severe thunderstorms along the route of flight and marginal visual flight rules conditions at the destination airport, with wind at 20 knots gusting to 30 knots, 4 miles visibility, moderate rain, and an overcast ceiling with thunderstorms in the vicinity. Although there were no hazardous weather advisories or convective SIGMETs active at the time the pilot received his preflight weather information, two of the air traffic controllers who worked the flight broadcast convective SIGMETs while the pilot was on frequency that affected the pilot's intended route of flight and called for thunderstorms with tops exceeding 40,000 ft. One of these SIGMETs was broadcast about 1 hour into the flight, and the second about 2 hours into the flight (about 40 minutes before the accident occurred). The pilot chose to continue along the flight route as weather conditions deteriorated, consistent with a common behavioral trap known as "get-there-itis."Review of weather and air traffic control radar data indicated that the airplane flew into a line of convective echoes and likely encountered instrument meteorological conditions, icing (including the possibility of supercooled large droplets), and moderate or greater turbulence about the time the airplane began the series of descending right turns that ultimately resulted in the in-flight breakup. The reduced Page 2 of 12 ERA17FA136visibility conditions and likely turbulent airmass encountered by the pilot are conducive to the development of spatial disorientation, and the in-flight breakup is consistent with the known effects of spatial disorientation. Given the severe weather conditions encountered, it is possible that the pilot's spatial disorientation was the result of an in-flight upset and significant challenges maintaining attitude control combined with the limited visibility.Toxicology testing of the pilot revealed the presence of amphetamine in lung and heart tissue. The pilot reported no conditions on his most recent application for a medical certificate, and whether the pilot was using amphetamine medicinally or illicitly could not be determined based on the available information.