The shooting was called in to police at about 1:30 a.m. from the 7000 block of Avenue F near 70th.
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According to HPD, the homeowner was in the kitchen when he saw a couple of suspicious people outside of his fence, so he grabbed his gun.
When he returned, one of the individuals was trying to push in the door.
Police say that's when the homeowner shot the woman multiple times, hitting her in the head.
The woman died at the scene. The second individual, a man in his 20s or 30s, is on the run.
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Officials say the homeowner called police and is cooperating with the investigation.
The man's girlfriend and his parents were in the home, but were not hurt.
The case will be referred to the Harris County grand jury, but HPD Sgt. Josh Horne told ABC13 at the scene there are no charges at this time.