Case: Patient 18, female, 18yo, congenital onset of symptoms

CasePresentingHPOs: HP:0003327, HP:0009053, HP:0002650, HP:0011713, HP:0003458 (axial muscle weakness, distal lower limb muscle weakness, scoliosis, left bundle branch block, EMG: myopathic abnormalities)

HPOsFreeText: respiratory involvement, NIV required from 7yo, normal CK levels

FamilyInfo: no family history

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.5655G>A (p.Ala1885=)

ClinVar: 378215, https://www.ncbi.nlm.nih.gov/clinvar/variation/378215/

gnomAD: absent

Case#: proband, young boy

DiseaseAssertion: muscular hypotonia

CasePresentingHPOs: HP:0008947, HP:0008947, HP:0002421, HP:0006829, HP:0008994, HP:0008981

"Infantile muscular hypotonia, delayed motor development, poor head control, severe muscular hypotonia, proximal muscle weakness in lower limbs, calf muscle hypertrophy"

CasePreviousTesting: ENMG at 3.5 months interpreted as normal, but at 6 months showed features of myopathy or muscular dystrophy

GenotypingMethod: Whole exome sequencing (WES) of the parents-offspring trio, Mutation was confirmed as de novo with Sanger sequencing. In silico analysis using both MutationTaster and MutPred Splice predicted the variant to disrupt splicing

Variant: NM_000257.4:c.5655G>A

ClinVar: 378215

CAID: CA16606815

gnomAD: https://gnomad.broadinstitute.org/variant/14-23883216-C-T

Total Allele Frequency: 0.00001193 European (non-Finnish): 0.00002637