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Mendeliome

Gene: KBTBD13

Green List (high evidence)

KBTBD13 (kelch repeat and BTB domain containing 13)
EnsemblGeneIds (GRCh38): ENSG00000234438
EnsemblGeneIds (GRCh37): ENSG00000234438
OMIM: 613727, Gene2Phenotype
KBTBD13 is in 6 panels

3 reviews

Bryony Thompson (Royal Melbourne Hospital)

I don't know

In 3 families with the Nemaline myopathy type 6 (NEM6) Dutch founder variant, c.1222C>T, p.Arg408Cys (KBTBD13 p.R408C), a cardiac phenotype was found to co-segregate with the variant (LOD score 6.02). In total, 65 NEM6 patients were evaluated of whom 12% presented with LV dilatation, 29% with LVEF < 50%, 8% with atrial fibrillation, 9% with ventricular tachycardia, and 20% with repolarization abnormalities. Mouse studies demonstrated that mice harbouring the Kbtbd13 p.R408C variant displayed mild diastolic dysfunction and Kbtbd13-deficient mice have systolic dysfunction. Currently, a cardiac phenotype has not been identified in individuals with any other pathogenic variants in KBTBD13.
Created: 2 Feb 2023, 11:53 p.m. | Last Modified: 2 Feb 2023, 11:53 p.m.
Panel Version: 1.654

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cardiomyopathy

Publications

Variants in this GENE are reported as part of current diagnostic practice

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

Well established gene-disease association of mono-allelic variants with nemaline myopathy, characterised by childhood onset of slowly progressive proximal muscle weakness, exercise intolerance, and slow movements with stiff muscles. Histopathologic changes seen on skeletal muscle biopsy include nemaline rods, cores devoid of oxidative enzyme activity, and predominance of hypertrophic type 1 fibers. There is no cardiac or respiratory involvement.

Note single report of bi-allelic variants causing a neuropathy and single report of heterozygous variant causing a milder, LGMD phenotype.
Created: 28 Aug 2020, 3:16 a.m. | Last Modified: 28 Aug 2020, 3:16 a.m.
Panel Version: 0.3963

Phenotypes
Nemaline myopathy 6, autosomal dominant, MIM# 609273; Hereditary motor neuropathy; late-onset limb girdle muscular dystrophy

Publications

Elena Savva (Victorian Clinical Genetics Services)

Green List (high evidence)

AR Hereditary motor neuropathy – single family with a homozygous missense (PMID: 31167812).*
AD late-onset limb girdle muscular dystrophy – single patient with a heterozygous missense (PMID: 30208948).*
*both papers demonstrate reduced protein expression

PMID: 31671076: recurring missense p.R408C causes increased actin filament stiffness and slowed relaxation kinetics. Concludes GOF mechanism.

Evidence of both LOF and GOF

Single example of AR inheritance
Created: 28 Aug 2020, 2:31 a.m. | Last Modified: 28 Aug 2020, 2:31 a.m.
Panel Version: 0.3961

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Nemaline myopathy 6, autosomal dominant, 609273; Hereditary motor neuropathy; late-onset limb girdle muscular dystrophy

Publications

Mode of pathogenicity
Other

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Victorian Clinical Genetics Services
Phenotypes
  • Nemaline myopathy 6, autosomal dominant, MIM# 609273
  • Hereditary motor neuropathy
  • late-onset limb girdle muscular dystrophy
OMIM
613727
Clinvar variants
Variants in KBTBD13
Penetrance
None
Publications
Panels with this gene

History Filter Activity

28 Aug 2020, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: kbtbd13 has been classified as Green List (High Evidence).

28 Aug 2020, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: KBTBD13 were changed from to Nemaline myopathy 6, autosomal dominant, MIM# 609273; Hereditary motor neuropathy; late-onset limb girdle muscular dystrophy

28 Aug 2020, Gel status: 3

Set publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Publications for gene: KBTBD13 were set to

28 Aug 2020, Gel status: 3

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: KBTBD13 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

17 Nov 2019, Gel status: 3

Created, Added New Source, Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

gene: KBTBD13 was added gene: KBTBD13 was added to Mendeliome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: KBTBD13 was set to Unknown