Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies
Gene: SMCHD1
For the purposes of testing, it makes sense to tier on a MONOALLELIC basis. For R381 referrals, detection of a single pathogenic variant in SMCHD1 would provoke further investigations to confirm a diagnosis of FSHD2, which would need to be done using other methods (methylation PCR). SMCHD1 has a digenic inheritance pattern and requires a permissive haplotype/methylation status for the FSHD1 locus (D4Z4/DUX4) in addition to a monoallelic pathogenic variant in SMCHD1. Email discussion with Rachael Mein, we decided that adding this gene to the R381 panel as monoallelic would be the best approach to ensure that this will be picked up in more speculative neuromuscular referrals.Created: 21 Feb 2024, 10:49 a.m. | Last Modified: 21 Feb 2024, 10:49 a.m.
Panel Version: 4.30
Mode of inheritance
Other
Variants in this GENE are reported as part of current diagnostic practice
Comment on list classification: Promoted from Red to Amber due to overall majority of Green reviews and clinical comments from from GLH representatives. As this is digenic, this gene has been made Amber rather than Green and tagged 'digenic'.Created: 28 Nov 2019, 4:17 p.m. | Last Modified: 29 Nov 2019, 10:34 a.m.
Panel Version: 1.184
FSHD2, differential diagnosis with LGMD.Created: 21 Oct 2019, 1:27 p.m. | Last Modified: 21 Oct 2019, 1:27 p.m.
Panel Version: 1.97
overlap LGMD phenotypeCreated: 10 May 2019, 3:38 p.m.
Digenic inheritanceCreated: 10 May 2019, 2:17 p.m.
Mode of inheritance
Other
Phenotypes
fascioscapulohumeral muscular dystrophy
Review and rating from Natalie Forrester (SWGLH - Bristol Genetics) on behalf of South West GLH for GMS Neurology specialist test group.Created: 30 Apr 2019, 11:45 a.m.
Only if for ddx with FSHDCreated: 30 Apr 2019, 11:24 a.m.
Mode of inheritance
Other - please specifiy in evaluation comments
Phenotypes
Fascioscapulohumeral muscular dystrophy 2, digenic, 158901
Digenic inheritance, SMCHD1 heterozygous mutation with permissive haplotype on DUX4. While WGS will not currently be able to fully diagnose FSHD2, detection of mutation in SCHMD1 will indicate that further testing is indicated. There is recognised clinical overlap between FSHD and LGMDs hence inclusion in this panel is indicated.Created: 29 Mar 2019, 2:02 p.m.
Mode of inheritance
Other
Phenotypes
fascioscapulohumeral muscular dystrophy
Comment when marking as ready: Associated with phenotype in OMIM and G2P. Numerous variants reported which are digenic with permissive D4Z4 haplotypeCreated: 26 Jul 2016, 1 p.m.
Comment on list classification: Digenic inheritanceCreated: 26 Jul 2016, 1 p.m.
Comment on mode of inheritance: Digenic with permissive D4Z4 haplotype of DUX4, that segregates independently in familiesCreated: 26 Jul 2016, 12:57 p.m.
Mode of inheritance
Unknown
Gene: smchd1 has been classified as Amber List (Moderate Evidence).
Gene: smchd1 has been classified as Green List (High Evidence).
Tag digenic tag was added to gene: SMCHD1.
Source Yorkshire and North East GLH was added to SMCHD1.
Phenotypes for gene: SMCHD1 were changed from Fascioscapulohumeral muscular dystrophy 2, digenic 158901 to Fascioscapulohumeral muscular dystrophy 2, digenic 158901; fascioscapulohumeral muscular dystrophy
Source NHS GMS was added to SMCHD1.
Source South West GLH was added to SMCHD1.
Comments from Fiona Karet included. A Green review for each gene relevant for this panel on the Gene Advisor download has been included.
This gene has been classified as Red List (Low Evidence).
This gene has been classified as Red List (Low Evidence).
Mode of inheritance for SMCHD1 was changed to Other - please specifiy in evaluation comments
SMCHD1 was created by sleigh
SMCHD1 was added to Limb girdle muscular dystrophypanel. Sources: Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,UKGTN