Malignant Hyperthermia Susceptibility
Gene: ASPHEnsemblGeneIds (GRCh38): ENSG00000198363
EnsemblGeneIds (GRCh37): ENSG00000198363
OMIM: 600582, Gene2Phenotype
ASPH is in 5 panels
1 review
Paul De Fazio (Victorian Clinical Genetics Services)
In a study of 103 individuals (63 affected from 34 families, plus 40 sporadic cases) who had either a sentinel event of EHI or MH, or else a positive CHCT and a first degree releative with EHI/MH, and where RYR1 and CACNA1S Sanger sequencing was negative, the following variants in ASPH were identified in unrelated individuals:
- c.161T > C in 2 members of a family with myalgias exacerbated by heat/exercise. One had elevated CK. Both had positive CHCT. An unaffected sibling did not have the variant. 27 hets in gnomad v2 / 17 hets in gnomad v3.
- c.445G>C in a patient with MH, myalgias and muscle cramps worsened by heat and exercise. 4 hets in gnomad v2 / 3 hets in gnomad v3. Non-coding in the MANE transcript.
- c.263A > C in a patient with EHI, diagnosed as MHN by in vitro contracture test. Absent from gnomad but non-coding in the MANE transcript.
- c.605A > G in a patient with EHI, diagnosed as MHN by in vitro contracture test. 223 hets in gnomad v2 / 120 hets in gnomad v3; no homs. Non-coding in the MANE transcript.
A zebrafish model and cell line functional studies supported pathogenicity of the c.161T > C and c.263A > C variants.
Sources: LiteratureCreated: 14 Jul 2022, 1:33 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Exertional heat illness; malignant hyperthermia susceptibility
Publications
Variants in this GENE are reported as part of current diagnostic practice
Details
- Mode of Inheritance
- MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
- Sources
-
- Expert Review Amber
- Phenotypes
-
- Exertional heat illness
- malignant hyperthermia susceptibility, MONDO:0018493, ASPH-related
- OMIM
- 600582
- Clinvar variants
- Variants in ASPH
- Penetrance
- None
- Publications
- Panels with this gene
History Filter Activity
Set Phenotypes
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Phenotypes for gene: ASPH were changed from Exertional heat illness; malignant hyperthermia susceptibility HP:0002047, ASPH-related to Exertional heat illness; malignant hyperthermia susceptibility, MONDO:0018493, ASPH-related
Entity classified by Genomics England curator
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Gene: asph has been classified as Amber List (Moderate Evidence).
Set Phenotypes
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Phenotypes for gene: ASPH were changed from Exertional heat illness; malignant hyperthermia susceptibility to Exertional heat illness; malignant hyperthermia susceptibility HP:0002047, ASPH-related
Entity classified by Genomics England curator
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Gene: asph has been classified as Amber List (Moderate Evidence).
Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes
Paul De Fazio (Victorian Clinical Genetics Services)gene: ASPH was added gene: ASPH was added to Malignant Hyperthermia Susceptibility. Sources: Literature Mode of inheritance for gene: ASPH was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ASPH were set to 35697689 Phenotypes for gene: ASPH were set to Exertional heat illness; malignant hyperthermia susceptibility Review for gene: ASPH was set to AMBER gene: ASPH was marked as current diagnostic