Formatting a Custom Penetrance File

File names may only contain numbers, letters, and dashes. Spaces and other special characters in the file name may cause an error.

The file can be uploaded as a plain text file or an excel file using the example penetrance file as a template. For the plain text file, the format of the pedigree file consists of 4 columns separated by a single space along with a header. An easy way to format pedigrees is to use Microsoft Excel and save the file as a tab delimited text file. The penetrance matrix has columns for the cumulative penetrance of the disease or trait in given age categories for men and women. Women are the first 7 rows, men are the next 7 rows. These columns are divided in rows by the sex and age group shown in the fourth column labeled “Comments”. For example, a 65 year old homozygous normal female would have a 0.05646 chance of having the disease according to the table below and a 52 year old heterozygous male has a 0.0063 chance of having the disease. For both text and Excel formats the 4 columns in order are:

  1. HomozygousNormal - This column is the cumulative penetrance of all phenotypes considered to be affected in individuals without the variant of interest (homozygous normal). For a rare disease or trait, the first column is close to the cumulative penetrance in the general population.
  2. Heterozygous - This column is the estimated cumulative penetrance of all phenotypes considered to be affected in individuals heterozygous for a pathogenic or causative variant.
  3. HomozygousMutant - This column is the cumulative penetrance of all phenotypes considered to be affected in individuals homozygous for a pathogenic variant. For dominant disease, cumulative incidence values may not be available. Our default is to copy the heterozygous cumulative incidence. Since homozygous and compound heterozygous individuals are extremely rare, this assumption is unlikely to alter calculations for the vast majority of families.
  4. Comments - This column shows the age classes that are build in to the FASTLINK software implementation used by AnalyzeMyVariant. This is only provided to help with file coding. Changing these numbers will not change the parameters in the FASTLINK calculations. It is common that literature will not present numbers for these exact age cutoffs. Penetrance at age X and cumulative incidence figures are sometimes helpful, as they may plot continuous lines from which age-based estimates can be extrapolated. If good values for cumulative penetrance are not known, you sometimes have to make assumptions and enter your educated guess. It is unlikely that small variations in penetrance estimates will meaningfully alter cosegregation likelihood values.

    5. Please visit the gene-specific penetrance information pages for examples.

    Example Penetrance File

    HomozygousNormal Heterozygous HomozygousMutant Comments
    0.000000885 0.001025896 0.001025896 << Class 1 female age < 20
    0.000040997 0.047524 0.047524 << Class 2 female 20 <= age < 30
    0.00189916 0.18042 0.18042 << Class 3 female 30 <= age < 40
    0.00878848 0.3736 0.3736 << Class 4 female 40 <= age < 50
    0.0275136 0.5752 0.5752 << Class 5 female 50 <= age < 60
    0.05646 0.6889 0.6889 << Class 6 female 60 <= age < 70
    0.0793 0.785 0.785 << Class 7 female 70 <= age
    7.58E-08 1.07368E-05 1.07368E-05 << Class 8 male age < 20
    0.0000012 0.00017 0.00017 << Class 9 male 20 <= age < 30
    0.000019 0.0012 0.0012 << Class 10 male 30 <= age < 40
    0.000085 0.003 0.003 << Class 11 male 40 <= age < 50
    0.00027 0.0062 0.0062 << Class 12 male 50 <= age < 60
    0.00067 0.012 0.012 << Class 13 male 60 <= age < 70
    0.0012 0.018 0.018 << Class 14 male 70 <= age