Table 1 CADRe rubric application

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