Limb-Girdle Muscular Dystrophy and Distal Myopathy

Gene: SMCHD1

Green List (high evidence)

SMCHD1 (structural maintenance of chromosomes flexible hinge domain containing 1)
EnsemblGeneIds (GRCh38): ENSG00000101596
EnsemblGeneIds (GRCh37): ENSG00000101596
OMIM: 614982, Gene2Phenotype
SMCHD1 is in 6 panels

3 reviews

Bryony Thompson (Royal Melbourne Hospital)

Green List (high evidence)

FSHD can have overlapping features with LGMD
Sources: Expert list
Created: 6 Jun 2022, 1:48 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Facioscapulohumeral muscular dystrophy MONDO:0001347

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)

Bosma arhinia microphthalmia syndrome (BAMS) is characterized by severe hypoplasia of the nose and eyes, palatal abnormalities, deficient taste and smell, inguinal hernias, hypogonadotropic hypogonadism with cryptorchidism, and normal intelligence. Choanal atresia is a feature. More than 30 unrelated individuals reported. Caused by gain of function missense variants with the extended ATPase domain.
Created: 26 Mar 2021, 9:32 p.m. | Last Modified: 26 Mar 2021, 9:32 p.m.
Panel Version: 0.6908
Comment when marking as ready: Note association with FSHD2 is postulated to have digenic inheritance, caused by the combination of a heterozygous mutation in the SMCHD1 gene (614982) on chromosome 18p and presence of a haplotype on chromosome 4 that is permissive for DUX4 (606009) expression.
Created: 20 Apr 2020, 8:52 a.m. | Last Modified: 20 Apr 2020, 8:52 a.m.
Panel Version: 0.2449

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Bosma arhinia microphthalmia syndrome, MIM# 603457; Arhinia, choanal atresia, microphthalmia MONDO:0011323

Publications

Mode of pathogenicity
Other

Teresa Zhao (Victorian Clinical Genetics Services)

Green List (high evidence)

Seven probands with FSHD reported to have LP/P variants, which all predicted to disrupt the structure and conformation of SMCHD1.

No particular geno-pheno correlation, but location of missense variants within the ATPase domain of MSCHD1 may contribute to the differences in phenotypic outcome (PMID: 31243061)
Created: 20 Apr 2020, 4:33 a.m. | Last Modified: 20 Apr 2020, 4:40 a.m.
Panel Version: 0.2383

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

Phenotypes
Bosma arhinia microphthalmia syndrome, MIM 603457; Fascioscapulohumeral muscular dystrophy 2, digenic

Publications

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Expert list
  • Expert Review Green
  • Victorian Clinical Genetics Services
Phenotypes
  • Facioscapulohumeral muscular dystrophy MONDO:0001347
OMIM
614982
Clinvar variants
Variants in SMCHD1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

6 Jun 2022, Gel status: 3

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: smchd1 has been classified as Green List (High Evidence).

6 Jun 2022, Gel status: 3

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: smchd1 has been classified as Green List (High Evidence).

6 Jun 2022, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Bryony Thompson (Royal Melbourne Hospital)

gene: SMCHD1 was added gene: SMCHD1 was added to Limb Girdle Muscular Dystrophy. Sources: Expert list Mode of inheritance for gene: SMCHD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SMCHD1 were set to 20301616 Phenotypes for gene: SMCHD1 were set to Facioscapulohumeral muscular dystrophy MONDO:0001347 Review for gene: SMCHD1 was set to GREEN gene: SMCHD1 was marked as current diagnostic