Congenital myopathy

Gene: TNPO3

I don't know

Comment on list classification: There are two unrelated families with congenital/ early-onset LGMD/ myopathy. However, only one patient from the large Spanish kindred was reported with myopathy before 5 years of age. Hence, this gene can only be rated amber with the current evidence. The 'watchlist' tag has been added to review this gene in light of any new evidence.

Created: 19 Jun 2026, 8:56 a.m. | Last Modified: 19 Jun 2026, 8:56 a.m.

Panel Version: 7.76

PMIDs: 23543484 & 23667635 (2013) reported a large multigenerational Spanish Pedigree with a novel form of autosomal dominant limb-girdle muscular dystrophy (LGMD) and they presented with limb-girdle and distal muscle weakness with variable distribution, severity, and rate of progression. A heterozygous single nucleotide deletion in TNPO3 gene (c.2771del) was identified in the family via whole-genome sequencing. Detailed clinical information was provided in PMID:23632945 for 29 patients of the family, where only one patient had onset before 5 years of age.

PMID:23667635 (2013) reported an additional sporadic case of an Italian female patient with young adult-onset LGMD phenotype and proximal weakness and had dystrophic biopsy with mitochondrial abnormalities (ragged-red fibres, COX-negative fibres).This patient was identified with a heterozygous variant in TNPO3 gene (c.2453G>A; p.Arg818Pro).

PMID:31071488 (2019) reported two individuals from a Hungarian family with an early-onset, slowly progressive muscular dystrophy. Both the female proband and her affected son had delayed early motor milestones and presented with progressive weakness of facial, bulbar, axial, and distal muscles especially of the lower extremities. Electromyography indicated myogenic damage and muscle biopsy from the proband showed myopathic alterations with sarcoplasmic masses and signs of mitochondrial dysfunction. Exome sequencing of the female proband identified a novel c.2767delC (p.Arg923AspfsTer17) variant in TNPO3, which was also identified in the affected son by Sanger sequencing; the unaffected son did not have the variant. It appears that PMID:31217819 describes the same Hungarian family form the descriptions.

PMID:31192305 (2019) reported the identification of a novel heterozygous variant c.2757delC (p.Arg920Glyfs*20) in TNPO3 gene in a three-generation Swedish family with congenital or early-onset myopathy and slow progression, causing proximal and less pronounced distal muscle weakness.

This gene has been associated with Muscular dystrophy, limb-girdle, autosomal dominant 2 in OMIM (MIM #608423, last accessed 19 June 2026). It is also classified as a 'Definitive' disease association by Muscular Dystrophies and Myopathies GCEP in ClinGen (https://search.clinicalgenome.org/CCID:008206)

Created: 18 Jun 2026, 8:19 a.m. | Last Modified: 19 Jun 2026, 8:53 a.m.

Panel Version: 7.75

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Muscular dystrophy, limb-girdle, autosomal dominant 2, OMIM:608423; autosomal dominant limb-girdle muscular dystrophy type 1F, MONDO:0012034

Publications

• 23543484
• 23632945
• 23667635
• 31071488
• 31192305
• 31217819

I don't know

associated with Dominant LGMD, in some cases this can have early/juvenile onset . This gene is green in LGMD panel

Created: 27 May 2026, 9:42 a.m. | Last Modified: 27 May 2026, 9:42 a.m.

Panel Version: 7.25

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted