Rhabdomyolysis and metabolic muscle disorders

Gene: AMPD1

Comment on list classification: This gene was promoted to Green and added to the diagnostic panel, however as per review by Zornitza Stark, it has since come to light that several variants reported in patients have a high frequency in the general population, calling into question their pathogenicity. Hence, tagging for GMS expert review to determine whether this gene should be demoted on this panel.

Created: 31 Jul 2025, 1:08 p.m. | Last Modified: 31 Jul 2025, 1:08 p.m.

Panel Version: 5.6

Red List (low evidence)

The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.

Created: 11 Mar 2026, 5:10 p.m. | Last Modified: 11 Mar 2026, 5:10 p.m.

Panel Version: 5.16

The rating of this gene has been updated to green and the mode of inheritance set to "BIALLELIC, autosomal or pseudoautosomal" following NHS Genomic Medicine Service approval.

Created: 11 Oct 2023, 11:17 a.m. | Last Modified: 11 Oct 2023, 11:41 a.m.

Panel Version: 3.37

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Red List (low evidence)

Variable age of onset ranging from infancy to adulthood (OMIM), however, no new publications supporting gene disease association. PMID: 21343608: Reported an infancy presenting with congenital hypotonia and muscle weakness. Variant reported in as VUS in ClinVar (as Q45*) and present in gnomad (1470 homozygotes) PMID: 11102975: Adult patient reported however variants reported R425H (also R458H) present in gnomad (3 homozygotes) and R388W (also R421W) present in gnomad (2 homozygotes).

The observation of a high number of homozygotes in gnomad together with the absence of new reports raises significant concerns about the pathogenicity of these variants.

Created: 1 Sep 2023, 9:28 a.m. | Last Modified: 1 Sep 2023, 9:28 a.m.

Panel Version: 3.35

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Myopathy due to myoadenylate deaminase deficiency (MIM#615511)

Publications

• 21343608
• 27296017

Green List (high evidence)

Comment on list classification: As recommended by Natalie Bibb and Andrew Swale, this gene is proposed for promotion to green as it is already green on the acute rhabdomyolysis panel (R419, https://panelapp.genomicsengland.co.uk/panels/1141/) based on recommendation by the NHS Genomic Medicine Service.

Created: 23 Aug 2023, 11:01 a.m. | Last Modified: 23 Aug 2023, 11:01 a.m.

Panel Version: 3.8

This gene has been associated with metabolic myopathy in OMIM (MIM #615511) and OMIM reports that rhabdomyolysis is seen in some patients.

Created: 23 Aug 2023, 10:57 a.m. | Last Modified: 23 Aug 2023, 10:57 a.m.

Panel Version: 3.7

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Myopathy due to myoadenylate deaminase deficiency, OMIM:615511

Comment when marking as ready: Associated with phenotype in OMIM, not in G2P / DD. At least 3 variants reported, however, issues raised in the publications about whether other factors are needed for the phenotype to be apparant

Created: 2 Dec 2016, 9:47 a.m.