15
6.8. Genetics and Family Screening
COR LOE
Recommendations
1 B-NR
4. In patients with HCM, genetic counseling by an expert in
the genetics of cardiovascular disease is recommended so
that risks, benefits, test results, and their clinical significance
can be reviewed and discussed with the patient in a shared
decision-making process.
1 B-NR
5. When performing genetic testing in a proband with HCM,
the initial tier of genes tested should include genes with
strong evidence to be disease-causing in HCM.*
1 B-NR
6. In first-degree relatives of patients with HCM, both clinical
screening (ECG and 2D echocardiogram) and cascade
genetic testing (when a pathogenic/likely pathogenic variant
has been identified in the proband) should be offered.
1 B-NR
7. In families where a sudden unexplained death has occurred
with a postmortem diagnosis of HCM, postmortem genetic
testing is beneficial to facilitate cascade genetic testing and
clinical screening in first-degree relatives.
1 B-NR
8. In patients with HCM who have undergone genetic
testing, serial reevaluation of the clinical significance of the
variant(s) identified is recommended to assess for variant
reclassification, which may impact diagnosis and cascade
genetic testing in family members (Figure 1, Figure 2).
1 B-NR
9. In affected families with HCM, preconception and prenatal
reproductive and genetic counseling should be offered.
2b B-NR
10. In adult patients with HCM, the usefulness of genetic testing
in the assessment of risk of SCD is uncertain.
2b B-NR
11. In patients with HCM who have a variant of uncertain
significance (VUS), the usefulness of clinical genetic testing
of phenotype-negative relatives for the purpose of variant
reclassification is uncertain.
3: No
benefit
B-NR
12. For patients with HCM who have undergone genetic testing
and were found to have no pathogenic variants (ie, harbor
only benign or likely benign variants), cascade genetic testing
of the family is not useful.
3: No
benefit
B-NR
13. Ongoing clinical screening is not indicated in genotype-
negative relatives in families with genotype-positive HCM,
unless the disease-causing variant is downgraded to a VUS,
likely benign, or benign variant during follow-up.
* Strong evidence HCM genes include, at the time of this publication: MYH7, MYBPC3,
TNNI3, TNNT2, TPM1, MYL2, MYL3, and ACTC1.
(cont'd)
