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Fetal anomalies

Gene: MYH3

Green List (high evidence)
MYH3 (myosin heavy chain 3)
EnsemblGeneIds (GRCh38): ENSG00000109063
EnsemblGeneIds (GRCh37): ENSG00000109063
OMIM: 160720, Gene2Phenotype
MYH3 is in 6 panels

2 reviews

Arina Puzriakova (Genomics England Curator)

Comment on mode of inheritance: MOI should be changed from 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' at the next GMS panel update.

Monoallelic variants are associated with distal arthrogryposis conditions including Freeman-Sheldon syndrome and Sheldon-Hall syndrome.

Monoallelic and biallelic variants also underlie Contractures, Pterygia, and Spondylocarpotarsal Fusion syndromes (CPSFS) which are characterised by extensive bony abnormalities in addition to congenital contractures. These features could be detected prenatally and therefore are relevant to this panel.

At least 3 unrelated recessive CPSFS cases have been reported with multiple contractures (PMID: 29805041). Additionally, two sibs from one family have been reported with distal arthrogryposis without additional features of CPSFS, who harboured two homozygous ultra-rare MYH3 variants (PMID: 38856159). Their presentation was assessed in a prenatal diagnostic setting. Overall this evidence supports an MOI of 'both mono- and biallelic' on this panel.
Created: 31 Jul 2025, 9:39 a.m. | Last Modified: 31 Jul 2025, 9:39 a.m.
Panel Version: 6.10
Created: 31 Jul 2025, 9:39 a.m.
Last Modified: 31 Jul 2025, 9:39 a.m.
Panel version: 6.10

Rebecca Foulger (Genomics England curator)

Green List (high evidence)

Additional evidence from PMID:30266093: AD/inherited het (mosaic mother) variant identified in MYH3 from fetal exome sequencing in Normand et al., 2018 (Clinical exome sequencing for fetuses with ultrasound abnormalities and a suspected Mendelian disorder, PMID:30266093).
Created: 18 Apr 2019, 3:55 p.m.
This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Confirmed that phenotype is fetally-relevant: keep on the Fetal anomalies panel as a Green gene.
Created: 24 Mar 2019, 4:30 p.m.
DDG2P rating in original PAGE list: Confirmed for DISTAL ARTHROGRYPOSIS TYPE 2B and Confirmed for DISTAL ARTHROGRYPOSIS TYPE 2A.
Created: 11 Dec 2018, 9:05 a.m.
In the original PAGE file, MOP listed as Uncertain for both disorders.
Created: 8 Nov 2018, 4:45 p.m.

Publications

Mode of pathogenicity
Other - please provide details in the comments

Created: 8 Nov 2018, 4:45 p.m.

Panel version: 0.185

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • PAGE DD-Gene2Phenotype
  • Expert Review Green
Phenotypes
  • Arthrogryposis, distal, type 2A (Freeman-Sheldon), OMIM:193700 (AD)
  • Arthrogryposis, distal, type 2B3 (Sheldon-Hall), OMIM:618436 (AD)
  • Contractures, pterygia, and spondylocarpostarsal fusion syndrome 1A, OMIM:178110 (AD)
  • Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B, OMIM:618469 (AR)
Tags
Q3_25_MOI
OMIM
160720
Clinvar variants
Variants in MYH3
Penetrance
None
Publications
Panels with this gene

History Filter Activity

31 Jul 2025, Gel status: 3

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: MYH3 were changed from DISTAL ARTHROGRYPOSIS TYPE 2B; DISTAL ARTHROGRYPOSIS TYPE 2A to Arthrogryposis, distal, type 2A (Freeman-Sheldon), OMIM:193700 (AD); Arthrogryposis, distal, type 2B3 (Sheldon-Hall), OMIM:618436 (AD); Contractures, pterygia, and spondylocarpostarsal fusion syndrome 1A, OMIM:178110 (AD); Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B, OMIM:618469 (AR)

31 Jul 2025, Gel status: 3

Set publications

Arina Puzriakova (Genomics England Curator)

Publications for gene: MYH3 were set to

31 Jul 2025, Gel status: 3

Set mode of inheritance

Arina Puzriakova (Genomics England Curator)

Mode of inheritance for gene: MYH3 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

31 Jul 2025, Gel status: 3

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q3_25_MOI tag was added to gene: MYH3.

8 Nov 2018, Gel status: 4

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Added phenotypes DISTAL ARTHROGRYPOSIS TYPE 2A for gene: MYH3

8 Nov 2018, Gel status: 4

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

Rebecca Foulger (Genomics England curator)

gene: MYH3 was added gene: MYH3 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: MYH3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: MYH3 were set to DISTAL ARTHROGRYPOSIS TYPE 2B