Supplementary Data: S2 Table

Case 95: Spanish, 1yo, Female

DiseaseAssertion: Hypertrophic Cardiomyopathy

CasePreviousTesting: Full Testing (MYBPC3, TNNT2, TNNI3, MYL2, MYL3, TPM1, ACTC1), additional testing listed in supplementary data table S1

CaseGenotypingMethod: genomic DNA obtained from blood or saliva, Next-gen sequencing panels of 55 or 78 genes

Variant: NM_000257.3(MYH7):c.2608C>T (p.Arg870Cys)

ClinVar: 161326, https://www.ncbi.nlm.nih.gov/clinvar/variation/161326/

gnomAD: 0.00002386, https://gnomad.broadinstitute.org/variant/14-23894049-G-A

MultipleGeneVariants:

(1) TTN Variant:

Variant: NM_133378.4:c.8920A>G

CAID: CA61002480, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_133378.4%3Ac.8920A%3EG

gnomAD: n/a

CaseCM1827: Female, 0 years diagnosis, Japan, Asian

CasePresentingHPOs: HP:0001639 (Hypertrophic cardiomyopathy)

HPOsFreeText: N/A

CaseNotHPOs: HP:0001939 (Abnormality of metabolism/homeostasis)

NotHPOsFreeText: Neuromuscular disease, Malformation syndromes

CaseAddInfo: No family history of cardiomyopathy or sudden death, Proband found in Supplementary Table 2, Mother tested negative for this variant

CasePreviousTesting: 8 patients with HCM and one with RCM were analyzed by NGS for the eight sarcomere-encoding genes and MYP.

CaseGenotypingMethod: Probands were subject to PCR amplification and direct sequencing of 64 cardiomyopathy-associated genes, including the eight sarcomere-encoding genes. The variants were then filtered for rarity and tested for pathogenicity.

Variant: NM_000257.3:c.2608C>T (p.Arg870Cys)

ClinVar: 161326 https://www.ncbi.nlm.nih.gov/clinvar/variation/161326/

gnomAD: Ashkenazi Jewish 9.923e-5, Overall 2.386e-5 https://gnomad.broadinstitute.org/variant/14-23894049-G-A

MultipleGeneVariants:

(1) MYBPC3 Variant

Variant: NM_000256.3:c.2285T>A (p.Val762Asp)

CAID: CA380320183 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000256.3%3Ac.2285T%3EA

gnomAD: Not in gnomAD

CaseCM1871: Male, 0 years diagnosis, Japan, Asian

CasePresentingHPOs: HP:0001639 (Hypertrophic cardiomyopathy)

HPOsFreeText: N/A

CaseNotHPOs: HP:0001939 (Abnormality of metabolism/homeostasis)

NotHPOsFreeText: Neuromuscular disease, Malformation syndromes

CaseAddInfo: No family history of cardiomyopathy or sudden death, Proband found in Supplementary Table 2, Mother shows negative for this variant with no symptoms

CasePreviousTesting: 8 patients with HCM and one with RCM were analyzed by NGS for the eight sarcomere-encoding genes and MYP.

CaseGenotypingMethod: Probands were subject to PCR amplification and direct sequencing of 64 cardiomyopathy-associated genes, including the eight sarcomere-encoding genes. The variants were then filtered for rarity and tested for pathogenicity.

Variant: NM_000257.3:c.2608C>T (p.Arg870Cys)

ClinVar: 161326 https://www.ncbi.nlm.nih.gov/clinvar/variation/161326/

gnomAD: Ashkenazi Jewish 9.923e-5, Overall 2.386e-5 https://gnomad.broadinstitute.org/variant/14-23894049-G-A