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Arthrogryposis

Gene: MYLPF

Amber List (moderate evidence)

MYLPF (myosin light chain, phosphorylatable, fast skeletal muscle)
EnsemblGeneIds (GRCh38): ENSG00000180209
EnsemblGeneIds (GRCh37): ENSG00000180209
OMIM: 617378, Gene2Phenotype
MYLPF is in 1 panel

2 reviews

Arina Puzriakova (Genomics England Curator)

I don't know

Comment on list classification: Given there are 6 families and different ethnic backgrounds, the biallelic form technically reaches the threshold for inclusion as Green. However, it should be considered that only the residue Cys157 has been implicated to date and the mechanism of pathogenicity is not clear.

Therefore rating Amber awaiting additional cases/functional evidence and further assessment by the GMS expert team to determine the most appropriate rating in view of the current evidence (tagged for 'expert-review')
Created: 26 Feb 2021, 11:35 a.m. | Last Modified: 26 Feb 2021, 11:35 a.m.
Panel Version: 3.74
Comment on mode of inheritance: Following consultation with Helen Brittain (Genomics England Clinical Team) it was agreed that in view of only 2 families with arthrogryposis and monoallelic variants in this gene there is currently not enough evidence to support inclusion of the monoallelic form. More cases or a delineation of the mechanism of pathogenicity are required before considering adding this as an MOI.
Created: 26 Feb 2021, 11:16 a.m. | Last Modified: 26 Feb 2021, 11:16 a.m.
Panel Version: 3.73
Associated with 'Arthrogryposis' phenotype in OMIM (MIM# 619110) and Gene2Phenotype ('probable' disease confidence rating for biallelic type; and 'possible' disease confidence for monoallelic type)

- PMID: 32707087 - 6 total families presenting distal arthrogryposis and homozygous MYLPF variants - 3 Pakistani families with a c.469T>C variant (shared ancestry indicating probable founder variant), and 3 families with a c.470G>T variant (1 of Polish ancestry and 2 Indian - haplotype analysis did not reveal a shared haplotype between the two).

Authors also identified two additional families with a very similar phenotype and different heterozygous variants (c.487G>A and c.98C>T, respectively). There is also a supportive zebrafish model where mutants display reduced trunk contractile force and complete pectoral fin paralysis.
Created: 26 Feb 2021, 11:01 a.m. | Last Modified: 26 Feb 2021, 11:01 a.m.
Panel Version: 3.72

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Arthrogryposis, distal, type 1C, OMIM:619110; Arthrogryposis, distal, type 1C, MONDO:0030847

Publications

Zornitza Stark (Australian Genomics)

I don't know

2 different homozygous variants reported in 6 consanguineous families with DA and an additional 2 different dominantly inherited variants in 2 families, with supporting animal model. Overall neither MOI data sufficient for Green rating.
Sources: Literature
Created: 4 Aug 2020, 10:53 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Distal arthrogryoposis

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Arthrogryposis, distal, type 1C, OMIM:619110
  • Arthrogryposis, distal, type 1C, MONDO:0030847
Tags
watchlist Q2_21_expert_review
OMIM
617378
Clinvar variants
Variants in MYLPF
Penetrance
None
Publications
Panels with this gene

History Filter Activity

26 Feb 2021, Gel status: 2

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag watchlist tag was added to gene: MYLPF.

26 Feb 2021, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: mylpf has been classified as Amber List (Moderate Evidence).

26 Feb 2021, Gel status: 0

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag Q2_21_expert_review tag was added to gene: MYLPF.

26 Feb 2021, Gel status: 0

Set mode of inheritance

Arina Puzriakova (Genomics England Curator)

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

8 Feb 2021, Gel status: 0

Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag watchlist was removed from gene: MYLPF.

8 Feb 2021, Gel status: 0

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag watchlist tag was added to gene: MYLPF.

8 Feb 2021, Gel status: 0

Set Phenotypes

Arina Puzriakova (Genomics England Curator)

Phenotypes for gene: MYLPF were changed from Distal arthrogryoposis to Arthrogryposis, distal, type 1C, OMIM:619110; Arthrogryposis, distal, type 1C, MONDO:0030847

4 Aug 2020, Gel status: 0

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

Zornitza Stark (Australian Genomics)

gene: MYLPF was added gene: MYLPF was added to Arthrogryposis. Sources: Literature Mode of inheritance for gene: MYLPF was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: MYLPF were set to 32707087 Phenotypes for gene: MYLPF were set to Distal arthrogryoposis Review for gene: MYLPF was set to AMBER