Not only physical characteristics and abilities can be inherited, but also the genetic predisposition to certain diseases. By analyzing genetic information, we can help to individualize preventive measures and, if necessary, adapt treatment options. Our ACMG module examines a list of genes compiled by the American College of Medical Genetics and Genomics and is relevant in preventive care. This way, potential health risks can be identified and responded to at an early stage.
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What is ACMG?
ACMG stands for American College of Medical Genetics and Genomics. An interdisciplinary group of experts in this association published a list for identifying and managing risks for selected genetic diseases.1 This list is regularly updated to include new findings from research. For the variants investigated and reported, there are established measures to reduce the risk or mitigate the disease. The focus lies on tumor diseases and cardiovascular diseases. However, the list also includes other genes whose variants can cause, for example, metabolic diseases.
The association of genes with certain disease patterns can also be found here.
Further information about the mentioned disease areas can be found in our modules tumor diseases, cardiovascular diseases, iron and copper storage disorders, hypercholesterolemia, eye diseases, malignant hyperthermia, familial diabetes, and metabolic diseases. In these modules, we have supplemented the genes in the ACMG guidelines for the individual disease areas with additional relevant genes based on our expertise.
Field Report
Alex R., 25 years old
Lifestyle: little exercise, smoker
Result: For Alex R., a variant in the gene LMNA was found that contributes to an increased risk for dilative cardiomyopathy.
Konsequenz: Alex R. now regularly attends check-ups with a cardiologist and has given up smoking. If necessary, measures can be taken at an early stage to mitigate the limitation in cardiac function.
“The test has opened my eyes to my increased risk for heart diseases. I am grateful to know this now and to be able to take countermeasures in time.”
How Does Genetic Risk Assessment Work?
Many factors contribute to the development of diseases. We help to determine the genetic risk. This allows known genetic variants to be reliably detected.
In the module ACMG, 84 genes are analyzed that are associated with an increased risk for tumor diseases, cardiovascular diseases, metabolic diseases, and others. In case of an increased risk, early detection measures and lifestyle adjustments can be useful. In the event of illness, therapies can be more target-oriented.
Genes Related to Cancer Phenotypes
Gene | Phenotype | OMIM ID | Inheritance | Variants to Report |
APC | Familial adenomatous polyposis | 175100 | AD | All P and LP |
RET | Familial medullary thyroid cancer | 155240 | AD | All P and LP Also associated with multiple endocrine neoplasia type 2 |
BRCA1 | Hereditary breast and/or ovarian cancer | 604370 | AD | All P and LP |
BRCA2 | Hereditary breast and/or ovarian cancer | 612555 | AD | All P and LP |
PALB2 | Hereditary breast and/or ovarian cancer | 114480 | AD | All P and LP |
SDHD | Hereditary paraganglioma-pheochromocytomasyndrome | 168000 | AD | All P and LP |
SDHAF2 | Hereditary paraganglioma-pheochromocytomasyndrome | 601650 | AD | All P and LP |
SDHC | Hereditary paraganglioma-pheochromocytomasyndrome | 605373 | AD | All P and LP |
SDHB | Hereditary paraganglioma-pheochromocytomasyndrome | 115310 | AD | All P and LP |
MAX | Hereditary paraganglioma-pheochromocytomasyndrome | 171300 | AD | All P and LP |
TMEM127 | Hereditary paraganglioma-pheochromocytomasyndrome | 171300 | AD | All P and LP |
BMPR1A | Juvenile polyposis syndrome | 174900 | AD | All P and LP |
SMAD4 | Juvenile polyposis syndrome | AD | All P and LP Also associated with hereditary hemorrhagic telangiectasia | |
TP53 | Li–Fraumeni syndrome | 151623 | AD | All P and LP |
MLH1 | Lynch syndrome (HNPCC) | 609310 | AD | All P and LP |
MSH2 | Lynch syndrome (HNPCC) | 120435 | AD | All P and LP |
MSH6 | Lynch syndrome (HNPCC) | 614350 | AD | All P and LP |
PMS2 | Lynch syndrome (HNPCC) | 614337 | AD | All P and LP |
MEN1 | Multiple endocrine neoplasia type 1 | 131100 | AD | All P and LP |
MUTYH | MUTYH-associated polyposis | 608456 | AR | P and LP (2 variants) |
NF2 | Neurofibromatosis type 2 | 101000 | AD | All P and LP |
STK11 | Peutz-Jeghers syndrome | 175200 | AD | All P and LP |
PTEN | PTEN hamartoma tumor syndrome | 158350 | AD | All P and LP |
RB1 | Retinoblastoma | 158350 | AD | All P and LP |
TSC1 | Tuberous sclerosis complex | 180200 | AD | All P and LP |
TSC2 | Tuberous sclerosis complex | 613254 | AD | All P and LP |
VHL | von Hippel-Lindau syndrome | 193300 | AD | All P and LP |
WT1 | WT1-related Wilms tumor | 194070 | AD | All P and LP |
AD = autosomal dominant; AR = autosomal recessive; LP = likely pathogenic; P = pathogenic
Genes Related to Cardiovascular Phenotypes
Gene | Phenotype | OMIM ID | Inheritance | Variants to Report |
FBN1 | Aortopathies | 154700 | AD | All P and LP |
TGFBR1 | Aortopathies | 609192 | AD | All P and LP Also associated with multiple endocrine neoplasia type 2 |
TGFBR2 | Aortopathies | 610168 | AD | All P and LP |
SMAD3 | Aortopathies | 613795 | AD | All P and LP |
ACTA2 | Aortopathies | 611788 | AD | All P and LP |
MYH11 | Aortopathies | 132900 | AD | All P and LP |
PKP2 | Arrhythmogenic right ventricularcardiomyopathy (A subcategory of ACM) | 609040 | AD | All P and LP |
DSP | Arrhythmogenic right ventricularcardiomyopathy (A subcategory of ACM) | 607450 | AD | All P and LP Also associated with dilated cardiomyopathy (DCM) as a primary disease |
DSC2 | Arrhythmogenic right ventricularcardiomyopathy (A subcategory of ACM) | 610476 | AD | All P and LP |
TMEM43 | Arrhythmogenic right ventricularcardiomyopathy (A subcategory of ACM) | 604400 | AD | All P and LP |
DSG2 | Arrhythmogenic right ventricularcardiomyopathy (A subcategory of ACM) | 610193 | AD | All P and LP |
RYR2 | Catecholaminergic polymorphic ventriculartachycardia | 604772 | AD | All P and LP |
CASQ2 | Catecholaminergic polymorphic ventriculartachycardia | 611938 | AR | P and LP (2 variants) |
TRDN | Catecholaminergic polymorphic ventriculartachycardia | 615441 | AR | P and LP (2 variants) Also associated with long QT syndrome |
TNNT2 | Dilated cardiomyopathy | 601494 | AD | All P and LP Also associated with hypertrophic cardiomyopathy (HCM) |
LMNA | Dilated cardiomyopathy | 115200 | AD | All P and LP Also associated with a skeletal myopathy (ie, myofibrillar myopathy) |
FLNC | Dilated cardiomyopathy | 617047 | AD | All P and LP Also associated with a skeletal myopathy (ie, myofibrillar myopathy) |
TTN | Dilated cardiomyopathy | 604145 | AD | All P and LP Only loss-of-function variants should be reported as a secondary finding |
BAG3 | Dilated cardiomyopathy | 613881 | AD | All P and LP Also associated with a skeletal myopathy (ie, myofibrillar myopathy) |
DES | Dilated cardiomyopathy | 604765 | AR | All P and LP Also associated with a skeletal myopathy (ie, myofibrillar myopathy) |
RBM20 | Dilated cardiomyopathy | 613172 | AD | All P and LP |
TNNC1 | Dilated cardiomyopathy | 611879 | AD | All P and LP |
PLN* | Dilated cardiomyopathy | 609909 | AD | All P and LP Also associated with hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC) |
COL3A1 | Ehlers-Danlos syndrome,vascular type | 130050 | AD | All P and LP |
LDLR | Familial hypercholesterolemia | 143890 | SD | All P and LP |
APOB | Familial hypercholesterolemia | 144010 | AD | All P and LP |
PCSK9 | Familial hypercholesterolemia | 603776 | AD | All P and LP |
MYH7 | Hypertrophic cardiomyopathy (Individuals with primary HCM may present in late stage disease with a DCM phenotype) | 192600 | AD | All P and LP Also associated with dilated cardiomyopathy (DCM) as a primary disease |
MYBPC3 | Hypertrophic cardiomyopathy (Individuals with primary HCM may present in late stage disease with a DCM phenotype) | 115197 | AD | All P and LP |
TNNI3 | Hypertrophic cardiomyopathy (Individuals with primary HCM may present in late stage disease with a DCM phenotype) | 613690 | AD | All P and LP |
TPM1 | Hypertrophic cardiomyopathy (Individuals with primary HCM may present in late stage disease with a DCM phenotype) | 115196 | AD | All P and LP |
MYL3 | Hypertrophic cardiomyopathy (Individuals with primary HCM may present in late stage disease with a DCM phenotype) | 608751 | AD | All P and LP |
ACTC1 | Hypertrophic cardiomyopathy (Individuals with primary HCM may present in late stage disease with a DCM phenotype) | 612098 | AD | All P and LP |
PRKAG2 | Hypertrophic cardiomyopathy (Individuals with primary HCM may present in late stage disease with a DCM phenotype) | 600858 | AD | All P and LP Pathogenic variants in this gene are associated with a metabolic storage disease that mimics HCM, but also can involve skeletal muscle. |
MYL2 | Hypertrophic cardiomyopathy (Individuals with primary HCM may present in late stage disease with a DCM phenotype) | 608758 | AD | All P and LP |
KCNQ1 | Long QT syndrome types 1 and 2 | 192500 | AD | All P and LP |
KCNH2 | Long QT syndrome types 1 and 3 | 613688 | AD | All P and LP |
SCN5A | Long QT syndrome 3, Brugada syndrome | 603830,601144 | AD | All P and LP Also associated with dilated cardiomyopathy (DCM) as a primary disease. |
CALM1 | Long QT syndrome type 14 | 616247 | AD | All P and LP |
CALM2 | Long QT syndrome type 15 | 616249 | AD | All P and LP |
CALM3 | Long QT syndrome type 16 | 618782 | AD | All P and LP |
AD = autosomal dominant; AR = autosomal recessive; SD = semidominant; LP = likely pathogenic; P = pathogenic
*New Genes according to ACMG SF v3.3; Lee et al., 2025, PMID: 40568962
Genes Related to Inborn Errors of Metabolism Phenotypes
Gene | Phenotype | OMIM ID | Inheritance | Variants to Report |
BTD | Biotinidase deficiency | 253260 | AR | P and LP (2 variants) |
CYP27A1* | Cerebrotendinous xanthomatosis | 213700 | AR | P and LP (2 variants) |
GLA | Fabry disease | 301500 | XL | All hemi-, het-, homozygous P and LP Gene also applies to the cardiovascular category |
OTC | Ornithine transcarbamylase deficiency | 311250 | XL | All hemi-, het-, homozygous P and LP |
GAA | Pompe disease | 232300 | AR | P and LP (2 variants) |
ABCD1* | X-linked adrenoleukodystrophy | 300100 | XL | homozygous or 2 het. P and LP (2 variants) |
AR = autosomal recessive; XL = X-linked; LP = likely pathogenic; P = pathogenic
*New Genes according to ACMG SF v3.3; Lee et al., 2025, PMID: 40568962
Genes Related to Miscellaneous Phenotypes
Gene | Phenotype | OMIM ID | Inheritance | Variants to Report |
HFE | Hereditary hemochromatosis | 235200 | AR | p.C282Y homozygotes only Transcript for the HFE gene is NM_000410.3 |
ACVRL1 | Hereditary hemorrhagic telangiectasia | 600376 | AD | All P and LP |
ENG | Hereditary hemorrhagic telangiectasia | 187300 | AD | All P and LP |
RYR1 | Malignant hyperthermia | 145600 | AD | All P and LP |
CACNA1S | Malignant hyperthermia | 601887 | AD | All P and LP |
HNF1A | Maturity-onset of diabetes of the young | 600496 | AD | All P and LP |
RPE65 | RPE65-related retinopathy | 204100,613794 | AR | P and LP (2 variants) |
ATP7B | Wilson disease | 277900 | AR | P and LP (2 variants) |
TTR | Hereditary TTR amyloidosis | 105210 | AD | All P and LP |
AD = autosomal dominant; AR = autosomal recessive; LP = likely pathogenic; P = pathogenic
Gene Set
Actionable Core Gene Set According to ACMG (3.3)
(PRV14, 84 Genes)
ABCD1, ACTA2, ACTC1, ACVRL1, APC, APOB, ATP7B, BAG3, BMPR1A, BRCA1, BRCA2, BTD, CACNA1S, CALM1, CALM2, CALM3, CASQ2, COL3A1, CYP27A1, DES, DSC2, DSG2, DSP, ENG, FBN1, FLNC, GAA, GLA, HFE, HNF1A, KCNH2, KCNQ1, LDLR, LMNA, MAX, MEN1, MLH1, MSH2, MSH6, MUTYH, MYBPC3, MYH11, MYH7, MYL2, MYL3, NF2, OTC, PALB2, PCSK9, PKP2, PLN ,PMS2, PRKAG2, PTEN, RB1, RBM20, RET, RPE65, RYR1, RYR2, SCN5A, SDHAF2, SDHB, SDHC, SDHD, SMAD3, SMAD4, STK11, TGFBR1, TGFBR2, TMEM127, TMEM43, TNNC1, TNNI3, TNNT2, TP53, TPM1, TRDN, TSC1, TSC2, TTN, TTR, VHL, WT1
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References
1 Miller, D. T. et al. ACMG SF v3.2 list for reporting of secondary findings in clinical exome and genome sequencing: A policy statement of the American College of Medical Genetics and Genomics (ACMG). Genetics in medicine : official journal of the American College of Medical Genetics 25, 100866; 10.1016/j.pediatrneurol.2021.03.005 (2023).