Now authorities are trying to piece together what may have happened to the couple's two step-grandchildren, who lived at the house but whose remains were not found in the rubble.
The Tennessee Bureau of Investigation on Wednesday issued an endangered child alert for the children, 9-year-old Chloie Leverette and 7-year-old Gage Daniel.
TBI spokeswoman Kristin Helm said the agency issued the alert "under an abundance of caution."
"As time moves on, we don't want to miss our opportunity to locate them if they were not in the house," Helm said.
The two children were initially believed to have perished in the intense fire, which firefighters battled overnight Sunday and early Monday.
Investigators said neighbors last saw the children Sunday evening, hours before a fire destroyed the home in Bedford County, about 40 miles southeast of Nashville.
Helm said the district attorney asked the agency to investigate the fatal fire and the whereabouts of the children. She said there is no evidence yet that the children were not in the house, but investigators are speaking with family members, friends and people at the children's school.
The State Fire Marshal's Office said in a statement that it has concluded "that there are no remains of the two children in the structure. The children's location at this time is unknown." Its investigators will determine a cause.
Bedford County Sheriff Randall Boyce said investigators did find the bodies of 72-year-old Leon "Bubba" McClaran and his 70-year-old wife, Molli McClaran. He said Monday that investigators had found three bodies, but now says one turned out to be that of a dog.
Forensic anthropologists and cadaver dogs searched through the rubble for the remaining bodies and the Tennessee Highway Patrol used a helicopter to search the surrounding area.
Even in an intense fire, some bones and teeth should remain, although finding them may be extremely difficult, said Dr. William Bass, who founded the Body Farm research center at the University of Tennessee in Knoxville, where researchers study the decomposition of corpses in a variety of circumstances to aid scientific and criminal research.
"When you cremate a body in a crematorium, and it is cooling down, when you open the door, you can still identify the bones even if they are children," he said.
A child's skeleton contains many more bones than an adult skeleton, and bones and teeth shrink in size when exposed to fire, so the bones that the investigators are looking for could be only a couple of inches long, he said.
Family members told The Associated Press that the McClarans were raising their step-grandchildren because they needed a home and described them as generous people who loved their family. Relatives of the McClarans said the girl also used the last name Pope.
The state Department of Children's Services investigated the mother of the two children and Daniel's father between 2006 and 2010, said spokesman Brandon Gee. Gee would not release the names of the parents.
He would not say why the parents were investigated, but said the agency was sharing information with law-enforcement officers involved in their search. He confirmed that the McClarans had custody of the two children, but he said DCS has never taken custody of them nor placed them in a home.