Two genetic experts have told the inquiry into the convictions of Kathleen Folbigg a "bad variant" likely led to the deaths of her two daughters.
However, the variant does not explain the deaths of her two sons, the inquiry heard.
Genetic variants identified in Katherine Folbigg and her daughters Laura and Sarah were not discovered until nine years after she was convicted of killing her four children in 2003.
Professors Mette Nyegaard and Michael Toft Overgaard are among authors of a scientific article that partially led to the inquiry, the second in three years, and appeared together at a hearing in Sydney on Tuesday.
The article, known as the Brohus article throughout the inquiry, was published after the 2019 inquiry.
It stops short of saying the identified variants caused the deaths of the two girls.
However, the inquiry under former NSW chief justice Tom Bathurst KC on Tuesday heard it very well could have.
"Would you say if it was 'likely' that the girls died by reason of the variant?" junior counsel assisting the inquiry Julia Roy asked the two Danish scientists.
"We think it is likely this mutation could have caused the death," Prof Overgaard said.
"It looks like a bad variant," Prof Nyegaard agreed.
The girls died long before the genetic variant was discovered.
"Is it inherent then in your conclusion that it is likely to have caused their deaths, the fact that they died?" Ms Roy asked.
"You would perhaps not predict a very early death for this particular impact," Prof Overgaard said.
The pair agreed that their conclusion was based only on their research and the material they had been provided, and no weight was given to the fact the two girls' brothers had also died.
Diaries and journals seized by police were a key factor in Folbigg's conviction and will be re-examined when the inquiry resumes in February.
The genetic variant affects the calcium-binding protein calmodulin, an early building block of life.
"It was regarded in the scientific community up until 2012 that variations in calmodulin were incompatible with life," Prof Overgaard said.
Prof Nyegaard identified variants in a large Swedish family, surprising the scientific community.
"There was a clear pattern ... we identified the first variant in calmodulin," Prof Nyegaard said.
She said the discovery was "extremely surprising".
Three different genes in the human genome produce calmodulin.
The variant identified in Folbigg, specifically CALM2 G114R, can affect the electrical activity of the heart.
Prof Overgaard said that variant was recently analysed.
"There's a significant impact on how calmodulin can bind to the (cardiac ion) channel," he said.
Mr Bathurst is being asked to form his own view on whether there is any reasonable doubt about Folbigg's guilt.
The inquiry comes 19 years after she was sentenced for the murder of three of her children and the manslaughter of a fourth.
The children, born separately between 1989 and 1997, were aged between 19 days and 18 months old when they died.
Folbigg was charged in April 2001.
The NSW Governor has ordered the re-examination following a petition from scientists calling for an inquiry due to new evidence.
Folbigg was sentenced to 40 years in prison in 2003, later reduced on appeal to 30 years with a non-parole period of 25.
She is not eligible for parole until 2028.