Fetal anomalies
Gene: DMPK
The rating of this gene has been updated to Red and the mode of inheritance set to 'Other' following NHS Genomic Medicine Service approval.Created: 30 Jan 2023, 4:26 p.m. | Last Modified: 30 Jan 2023, 4:26 p.m.
Panel Version: 2.10
Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism. MOI should be changed to 'Other' to maintain consistency with other panelsCreated: 9 Nov 2021, 3:29 p.m. | Last Modified: 9 Nov 2021, 3:29 p.m.
Panel Version: 1.805
Comment on list classification: This gene should be demoted from Green to Red at the next GMS review due to the disease-causing mechanism - genetic defect is an amplified trinucleotide CTG repeat in the 3'UTR (currently NGS unreportable), rather than SNVs within the gene. Evidence level for this is high - it is a confirmed DD gene for DYSTROPHIA MYOTONICA TYPE 1.
DMPK_CTG STR will be added to the panel to capture this entity and ensure that cases are detected.Created: 9 Jul 2021, 12:20 p.m. | Last Modified: 9 Jul 2021, 12:38 p.m.
Panel Version: 1.687
Causes myotinic dystrophy only due to STR expansion, not SNVs.Created: 30 Jun 2021, 11:04 a.m. | Last Modified: 30 Jun 2021, 11:06 a.m.
Panel Version: 1.679
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
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 Green. Additional notes from clinical review: Note of caution that repeat expansion is clinically-relevant and not detectable on exome. Only relevant prenatally if it is a large expansion. A small expansion has adult onset and would be an incidental finding.Created: 24 Mar 2019, 4:30 p.m.
DDG2P rating in original PAGE list: Confirmed for DYSTROPHIA MYOTONICA TYPE 1Created: 11 Dec 2018, 9:04 a.m.
In the original PAGE file, MOP listed as Dominant negative.Created: 8 Nov 2018, 4:45 p.m.
Mode of pathogenicity
Other - please provide details in the comments
Tag Q3_21_MOI was removed from gene: DMPK. Tag Q3_21_rating was removed from gene: DMPK. Tag Q3_21_expert_review was removed from gene: DMPK.
Source Expert Review Red was added to DMPK. Source NHS GMS was added to DMPK. Mode of inheritance for gene DMPK was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to Other Rating Changed from Green List (high evidence) to Red List (low evidence)
Tag Q3_21_expert_review tag was added to gene: DMPK.
Phenotypes for gene: DMPK were changed from DYSTROPHIA MYOTONICA TYPE 1 to Myotonic dystrophy 1, OMIM:160900
Mode of pathogenicity for gene: DMPK was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Tag Q3_21_MOI tag was added to gene: DMPK.
Mode of inheritance for gene: DMPK was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Gene: dmpk has been classified as Green List (High Evidence).
Tag nucleotide-repeat-expansion tag was added to gene: DMPK. Tag currently-ngs-unreportable tag was added to gene: DMPK. Tag Q3_21_rating tag was added to gene: DMPK.
gene: DMPK was added gene: DMPK was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: DMPK was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene: DMPK were set to DYSTROPHIA MYOTONICA TYPE 1