Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies

Gene: SVIL

I don't know

Comment on list classification: There are 4 individuals from 2 unrelated families reported in literature with homozygous nonsense variants in SVIL, diagnosed with myopathy with myofibrillar disorganization. This gene should be rated Amber on Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies until more evidence emerges.

Created: 24 Nov 2025, 1:10 p.m. | Last Modified: 24 Nov 2025, 1:11 p.m.

Panel Version: 5.22

PMID: 32779703 Hedberg-Oldfors et al., 2020
Report of 2 unrelated consanguineous families with myopathy with myofibrillar disorganization. Muscle biopsy showed Structural myopathy with prominent lobulated type 1 fibres, myofibrillar disintegration and signs of altered proteostasis/impaired autophagy in all 4 affected individuals. All patients showed increased creatine kinase levels, but no or minor muscle weakness. Variable presentation, including muscle pain, slowly progressive stiffness, exercise intolerance, as well as distinct anomalies of neck and shoulder girdle; 3/4 patients presented with contractures. Very mild heart involvement.
Seq method: WES/ targeted exome with Sanger confirmation.
Family 1: Lebanese, 2 sibs affected, both homozygous for c.4812C>A, p.(Tyr1604*) - variant not in gnomAD v4.1.0. Symptom onset: childhood/adolescence.
Family 2: Turkish, 2 sibs affected, both homozygous for c.3578_3579del, p.(Val1193Glufs*46) - variant not in gnomAD v4.1.0; symptoms onset at birth/ in infancy.

SVIL is associated with AR Myofibrillar myopathy 10, MIM: 619040 (OMIM accessed 24th Nov 2025).
Sources: Literature

Created: 24 Nov 2025, 12:50 p.m. | Last Modified: 24 Nov 2025, 1:46 p.m.

Panel Version: 5.22

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Myofibrillar myopathy 10, OMIM:619040; myofibrillar myopathy 10, MONDO:0033620

Publications

• 32779703