A method to detect one or more genetic variations and/or amount of genetic variation in a subject, comprising: (a) sequencing nucleic acid molecules in a cfDNA sample of the subject with a genetic analyzer to generate a first set of sequence reads at a first time point; (b) comparing the first set of sequence reads with at least a second set of sequence reads obtained at least at a second time point before the first time point to yield a comparison of first set of sequence reads and the at least the second set of sequence reads, wherein the sequence reads are from a plurality of samples collected over a plurality of time points and two of the sampling time points are separated by at least 1 day, 1 week, 2 weeks, 3 weeks, one month, or one year; (c) using the comparison to update a diagnostic confidence indication accordingly by: (i) increasing the diagnostic confidence indication if information obtained from the first set of sequence reads at the first time point corroborates information obtained from the at least the second set of sequence reads at the second time point, (ii) decreasing the diagnostic confidence indication if information obtained from the first set of sequence reads at the first time point does not corroborate or conflicts with information obtained from the at least the second set of sequence reads at the second time point, or (iii) leaving as is the diagnostic confidence indication in a subsequent characterization for de novo information, which diagnostic confidence indication is indicative of a probability of identifying one or more genetic variations in a cfDNA sample of the subject, wherein the diagnostic confidence indication is further adjusted based on the detection of co-variate variations; and (d) detecting a presence or absence of the one or more genetic variations and/or amount of genetic variation in nucleic acid molecules in a cfDNA sample of the subject based on the diagnostic confidence indication, wherein the diagnostic confidence indication is a number, a rank, a score, a degree or a value assigned to indicate the presence of the one or more genetic variants and how much that presence is trusted. (a) sequencing nucleic acid molecules in a cfDNA sample of the subject with a genetic analyzer to generate a first set of sequence reads at a first time point; (b) comparing the first set of sequence reads with at least a second set of sequence reads obtained at least at a second time point before the first time point to yield a comparison of first set of sequence reads and the at least the second set of sequence reads, wherein the sequence reads are from a plurality of samples collected over a plurality of time points and two of the sampling time points are separated by at least 1 day, 1 week, 2 weeks, 3 weeks, one month, or one year; (c) using the comparison to update a diagnostic confidence indication accordingly by: (i) increasing the diagnostic confidence indication if information obtained from the first set of sequence reads at the first time point corroborates information obtained from the at least the second set of sequence reads at the second time point, (ii) decreasing the diagnostic confidence indication if information obtained from the first set of sequence reads at the first time point does not corroborate or conflicts with information obtained from the at least the second set of sequence reads at the second time point, or (iii) leaving as is the diagnostic confidence indication in a subsequent characterization for de novo information, which diagnostic confidence indication is indicative of a probability of identifying one or more genetic variations in a cfDNA sample of the subject, wherein the diagnostic confidence indication is further adjusted based on the detection of co-variate variations; and (i) increasing the diagnostic confidence indication if information obtained from the first set of sequence reads at the first time point corroborates information obtained from the at least the second set of sequence reads at the second time point, (ii) decreasing the diagnostic confidence indication if information obtained from the first set of sequence reads at the first time point does not corroborate or conflicts with information obtained from the at least the second set of sequence reads at the second time point, or (iii) leaving as is the diagnostic confidence indication in a subsequent (d) detecting a presence or absence of the one or more genetic variations and/or amount of genetic variation in nucleic acid molecules in a cfDNA sample of the subject based on the diagnostic confidence indication,