Supplementary Data: Table S3

Case 90:

DiseaseAssertion: left ventricular noncompaction

CasePresentingHPOs: HP:0030682 (left ventricular noncompaction)

CaseHPOFreeText: >7yo, able to hold breath, non compacted segment = distinct 2-layered appearance of trabeculated and compacted myocardium, NC/C ratio > 2.3:1

CasePreviousTesting: Cardiac MRI using 17-segment model of LV segmentation, ECG, transthoracic echocardiography, full testing (MYBPC3, TNNT2, TNNI3, MYL2, MYL3, TPM1, ACTC1), additional testing listed in supplementary data tables S1 and S2.

CaseGenotypingMethod: WES, variant enrichment analysis

Variant: NM_000257.3(MYH7):c.745C>T (p.Arg249Ter)

ClinVar: 407183, https://www.ncbi.nlm.nih.gov/clinvar/variation/407183/

gnomAD: 0.000003977, https://gnomad.broadinstitute.org/variant/14-23900678-G-A

MultipleGeneVariants:

(1) TPM1 Variant:

Variant: NM_001018004.1(TPM1):c.775A>G (p.Lys259Glu)

ClinVar: 43687, https://www.ncbi.nlm.nih.gov/clinvar/variation/43687/

gnomAD: 0.0008382, https://gnomad.broadinstitute.org/variant/15-63363291-A-G

(2) PRKAG2 Variant:

Variant: p.Lys133Ile no ClinVar or CAID

CaseP1-GAA: Male, ethnicity = North African, country origin = Morocco

CasePresentingHPOs: HP:0010899, HP:0010916, HP:0003236

HPOsFreeText: enzyme activity = 0.61, CPK = 448 U/L, ALT = 48 U/L, AST = 98 U/L, CRIM positive

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: heterozygote, variants in trans. Patient underwent ERT.

CasePreviousTesting: initial and confirmatory DBS, biochemical tests, echocardiography

CaseGenotypingMethod: mutation analyses

Variant1: NM_000152.4(GAA):c.-32-13T>G

Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: n/a

Variant2: NM_000152.4(GAA):c.236_246delCCACACAGTGC (p.Pro79Argfs)

ClinVar: 371302, https://www.ncbi.nlm.nih.gov/clinvar/variation/371302/

gnomAD: n/a

Patient5: female

CasePresentingHPOs: HP:0001270

HPOsFreeText: CRIM negative, Anti-rh GGA antibodies maximum titer = 1:25.600, infusion associated reaction, heat normalization

CaseNotHPOs: HP:0004887, HP:0025156, HP:0001371

CaseAddInfo: homozygous variants in trans, symptom onset and diagnosis at 1yo, ERT at 2yo. Died due to infusion reaction with ERT.

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant: NM_000152.4(GAA):c.236_246delCCACACAGTGC (p.Pro79Argfs)

ClinVar: 371302, https://www.ncbi.nlm.nih.gov/clinvar/variation/371302/

gnomAD: n/a

Patient13: female

CasePresentingHPOs: HP:0004887, HP:0011471, HP:0001270, HP:0002546, HP:0000365

HPOsFreeText: CRIM positive, tracheostomy, partial heart normalization

CaseNotHPOs: HP:0001371

NotHPOsFreeText: infusion associated reaction

CaseAddInfo: variants in trans, symptom onset at 6yo, diagnosis and ERT at 11yo

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.236_246delCCACACAGTGC (p.Pro79Argfs)

ClinVar: 371302, https://www.ncbi.nlm.nih.gov/clinvar/variation/371302/

gnomAD: n/a

Variant2: NM_000152.4(GAA):c.1927G>A (p.Gly643Arg)

ClinVar: 4023, https://www.ncbi.nlm.nih.gov/clinvar/variation/4023/

gnomAD: 5.884e-05, http://exac.broadinstitute.org/variant/17-78086713-G-A