. 2022 Dec 15;14:141. doi: 10.1186/s13073-022-01142-7

Table 1.

Valid disease state combinations and corresponding weighting factors for estimating disease state rates

Variant frequencies provided	Required weighting factors
Familial ( $M_{F}$ ), Sporadic ( $M_{S}$ )	$W_{F} = P (F \| A)$ , $W_{S} = P (S \| A)$
Familial ( $M_{F}$ ), Unaffected ( $M_{U}$ )	$W_{F} = P (F \| A) \times P {(A)}^{pop}$ , $W_{U} = 1 - P {(A)}^{pop}$
Sporadic ( $M_{S}$ ), Unaffected ( $M_{U}$ )	$W_{S} = P (S \| A) \times P {(A)}^{pop}$ , $W_{U} = 1 - P {(A)}^{pop}$
Familial ( $M_{F}$ ), Sporadic ( $M_{S}$ ), Unaffected ( $M_{U}$ )	$W_{F} = P (F \| A) \times P {(A)}^{pop}$ , $W_{S} = P (S \| A) \times P {(A)}^{pop}$ , $W_{U} = 1 - P {(A)}^{pop}$
Affected ( $M_{A}$ ), Unaffected ( $M_{U}$ )	$W_{A} = P {(A)}^{pop}$ , $W_{U} = 1 - P {(A)}^{pop}$

Variant frequencies provided

Required weighting factors

Familial ( $M_{F}$ ),

Sporadic ( $M_{S}$ )

$W_{F} = P (F | A)$ ,

$W_{S} = P (S | A)$

Familial ( $M_{F}$ ),

Unaffected ( $M_{U}$ )

$W_{F} = P (F | A) \times P {(A)}^{pop}$ ,

$W_{U} = 1 - P {(A)}^{pop}$

Sporadic ( $M_{S}$ ),

Unaffected ( $M_{U}$ )

$W_{S} = P (S | A) \times P {(A)}^{pop}$ ,

$W_{U} = 1 - P {(A)}^{pop}$

Familial ( $M_{F}$ ),

Sporadic ( $M_{S}$ ),

Unaffected ( $M_{U}$ )

$W_{F} = P (F | A) \times P {(A)}^{pop}$ ,

$W_{S} = P (S | A) \times P {(A)}^{pop}$ ,

$W_{U} = 1 - P {(A)}^{pop}$

Affected ( $M_{A}$ ),

Unaffected ( $M_{U}$ )

$W_{A} = P {(A)}^{pop}$ ,

$W_{U} = 1 - P {(A)}^{pop}$

The defined weighting factors are used in Step 1 of the penetrance estimation approach, as described in Fig. 1 and Additional File 1: Sect. 1.1 $M_{F, S, U, A}$ = variant frequencies in the familial, sporadic, unaffected, and affected states; $W_{F, S, U, A}$ = weighting factors for the familial, sporadic, unaffected, and affected states; $P {(A)}^{pop}$ = the probability of a member of the sampled population being affected; $P (F | A)$ = disease familiality rate; $P (S | A)$ = disease sporadic rate