Case: Patient 12, male, 7yo

CasePresentingHPOs: HP:0030682 (left ventricular noncompaction)

HPOsFreeText: CK = 1400U/l

CaseNotHPOs:

NotHPOsFreeText: no muscle symptoms, no respiratory or cardiac involvement

FamilyInfo: family history, pedigree in figure 1

DiseaseEntity: no assertion

InheritancePattern: no assertion

CasePreviousTesting: see below

CaseGenotypingMethod: 9 cases underwent targeted Sanger sequencing of MYH7, 12 cases underwent Motorplex analysis (NGS of 93 myopathy-related genes - PMID:25214167), all MYH7 variants confirmed via Sanger sequencing, segregation analysis performed on available family members, which cases received which sequencing technique is not specified

Variant: NM_000257.4(MYH7):c.5401G>A (p.Glu1801Lys)

ClinVar: 43069, https://www.ncbi.nlm.nih.gov/clinvar/variation/43069/

gnomAD: absent

Case391: Female, 0.83 years onset, Japan, Asian

DiseaseAssertion: Left ventricular noncompaction

CasePresentingHPOs: HP:0030682, HP:0025169, HP:0001635 (Left ventricular noncompaction, Left ventricular systolic dysfunction, Heart failure)

HPOsFreeText: Left Ventricular Ejection Fraction at 38%, LVDD-Z score at 2.6785

CaseNotHPOs: HP:0011675 (Arrhythmia)

NotHPOsFreeText: Congenital heart disease with significant hemodynamic changes

CaseAddInfo: No family history

CasePreviousTesting: Genes tested include the 8 sarcomere genes as well as 65 more listed in Table S1.

CaseGenotypingMethod: Genomic DNA was extracted from whole blood from each of the probands. Next Generation Sequencing of 73 genes related to cardiac function was performed, incorporating PCR amplification, and any variants found were subjected to filtering for frequency and pathogenicity. Any variants suggested to be pathogenic were confirmed by Sanger sequencing afterwards.

Variant: NM_000257.3:c.5401G>A (p.Glu1801Lys)

ClinVar: 43069 https://www.ncbi.nlm.nih.gov/clinvar/variation/43069/

gnomAD: Not in gnomAD

Case: male, 44yo at diagnosis

DiseaseAssertion: Dilated cardiomyopathy (DCM)

CasePresentingHPOs: HP:0012664, HP:0001635, HP:0100598, HP:0001324, HP:0003388 (reduced ejection fraction, heart failure, pulmonary oedema, muscle weakness, fatigability)

HPOsFreeText: reduced LVEF (=29%), diagnosed with congenital myopathy at 36yo, LVIDD = 74mm, creatine kinase < 600 U/l, ICD implantation, waiting heart transplantation at 48yo

CaseNotHPOs:

NotHPOsFreeText: anti-tachycardia pacing or shock therapy from the ICD

CasePreviousTesting: ACTA1, BIN1, DNM2, MYH7, MTM1, NEB, RYR1, SCN4A, SEPN1, TPM2, TPM3

CaseGenotypingMethod: PCR amplification of exons of genes investigated and Sanger sequencing or NGS

Variant: NM_000257.4(MYH7):c.5401G>A (p.Glu1801Lys)

ClinVar: 43069, https://www.ncbi.nlm.nih.gov/clinvar/variation/43069/

gnomAD: absent

CaseII2: 65 year old male

DiseaseAssertion: left ventricular non compaction cardiomyopathy

FamilyInfo: three family members presenting with the same MYH7 mutation

CasePresentingHPOs: HP:0012764, HP:0002515, HP:0003376, HP:0003307, HP:0003391, HP:0003547

"Orthopnea, Waddling gait, Steppage gait, Hyperlordosis, Gowers sign, Shoulder girdle muscle weakness"

CaseHPOFreeText: shortness of breath during exertion, foot drop, At lower limbs weakness and hypotrophy were severe in distal muscles and moderate in proximal muscles

CaseNotHPOs:

CaseNotHPOFreeText:

CasePreviousTesting: molecular analysis for ACTA1 and ITGA7 was performed, resulted negative. Molecular analysis for DES, LMNA and MYH7 genes were carried out

GenotypingMethod: mutation screening, primers flanking the intron-exon junctions of each MYH7 exon, the 5′ and 3′ UTR

Variant: NM_000257.4:c.5401G>A

ClinVar: 43069

CAID: CA016087

gnomAD: not found