Table 1.

CADRe rubric application

Category	Genes included	Rationale
Genes included in the American College of Medical Genetics secondary findings (ACMG SF) v2.0 [24]	Cancer risk: BRCA1, BRCA2, MLH1, MSH2, MSH6, PMS2, RET, BMPR1A, SMAD4, TP53, MEN1, TSC1, TSC2, PTEN, STK11, APC, VHL, NF2, RB1, SDHD, SDHAF2, SDHC, SDHB, MUTYH, WT1 Cardiovascular risk: FBN1, TGFBR1, TGFBR2, SMAD3, ACTA2, MYH11, COL3A1, LDLR, APOB, PCSK9, RYR2, KCNQ1, KCNH2, SCN5A, MYBPC3, MYH7, TNNT2, TNNI3, TPM1, MYL3, ACTC1, PRKAG2, MYL2, LMNA, PKP2, DSP, DSC2, TMEM43, DSG2 Metabolic: GLA, OTC, ATP7B Other: RYR1, CACNA1S	Well described, evidence for medical intervention, commonly evaluated [25]
Moderate penetrance cancer risk	Breast cancer risk: ATM, CHEK2, PALB2, BARD1 Colon cancer risk: GREM1, POLD1, POLE	Commonly included on genetic testing panels with similar phenotypes as some genes in the ACMG SF v2.0 [24, 26]
Moderate evidence cardiomyopathy risk [27]	Cardiovascular risk: CSRP3, TNNC1, JPH2	Commonly included on genetic testing panels with similar phenotypes as some genes in the ACMG SF v2.0 [24, 26]
Genes that have limited evidence of gene-disease association for hypertrophic cardiomyopathy [27]	Limited evidence hypertrophic cardiomyopathy risk: TTN, KLF10, MYPN, ANKRD1	Included as preliminary evidence add-on genes on genetic testing panels [26]
Genes that have refuted or disputed evidence of gene-disease association for breast cancer risk [28]	BRIP1, RAD51C	Included on broad cancer panels, may not relate to indication for testing, and yet would have management recommendations if a pathogenic/likely pathogenic variant is identified [26]
Genes associated with risk for neurodegenerative disorders	HTT, APP, PSEN1, PSEN2, MAPT, GRN, SOD1, c9orf72, ApoE	Not clinically actionable
Exome	Not Applicable	Increasingly common genetic testing in which multiple genetic conditions are under consideration