DDG2P
Gene: DMPK
Comment on list classification: This gene has now been demoted from Green to Red despite having a gene-disease association with 'definitive' rating in the DD panel in G2P. This is because the disease-causing mechanism is an amplified trinucleotide CTG repeat in the 3'UTR (currently NGS unreportable), rather than SNVs within the gene.Created: 9 Oct 2023, 5:57 p.m. | Last Modified: 9 Oct 2023, 5:57 p.m.
Panel Version: 3.72
The DDG2P confidence category for the disease DYSTROPHIA MYOTONICA TYPE 1, OMIM:160900 is definitive. The allelic requirement and mutation consequence are monoallelic_autosomal and altered gene product structure.Created: 4 Oct 2023, 5:08 p.m. | Last Modified: 4 Oct 2023, 5:08 p.m.
Panel Version: 3.12
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
DYSTROPHIA MYOTONICA TYPE 1, OMIM:160900
Mode of pathogenicity
Other
Leaving the GMS tags on this gene as a reminder that this gene should be demoted to red after the next update to make the panel be in line with the latest Developmental Disorders panel in Gene2Phenotype. Although the gene may have a strong rated gene-disease association in Gene2Phenotype for PanelApp and the Genomics England pipeline it should be the STR that is rated green.
Leaving it green for now is not considered high clinical risk.Created: 27 Jul 2022, 1:56 p.m. | Last Modified: 27 Jul 2022, 1:56 p.m.
Panel Version: 2.76
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, 3:31 p.m. | Last Modified: 9 Nov 2021, 3:31 p.m.
Panel Version: 2.53
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.
However, the evidence level for this expansion is high (it is a confirmed DD gene for DYSTROPHIA MYOTONICA TYPE 1), and as DDG2P is a component of the Paediatric disorders super panel, the DMPK_CTG STR will be added to the panel to capture this entity and ensure that cases are detected.Created: 9 Jul 2021, 12:35 p.m. | Last Modified: 9 Jul 2021, 12:35 p.m.
Panel Version: 2.35
Causes myotinic dystrophy only due to STR expansion, not SNVs.Created: 30 Jun 2021, 11:05 a.m. | Last Modified: 30 Jun 2021, 11:06 a.m.
Panel Version: 2.29
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Original DDG2P rating: confirmed. DDG2P mode of pathogenicity: dominant negativeCreated: 19 Nov 2018, 11:29 a.m.
Tag Q3_21_MOI was removed from gene: DMPK. Tag Q3_21_rating was removed from gene: DMPK.
Gene: dmpk has been classified as Red List (Low Evidence).
Phenotypes for gene: DMPK were changed from DYSTROPHIA MYOTONICA TYPE 1, OMIM:160900 to DYSTROPHIA MYOTONICA TYPE 1, OMIM:160900
Phenotypes for gene: DMPK were changed from DYSTROPHIA MYOTONICA TYPE 1, OMIM:160900 to DYSTROPHIA MYOTONICA TYPE 1, OMIM:160900
Phenotypes for gene: DMPK were changed from DYSTROPHIA MYOTONICA TYPE 1 160900 to DYSTROPHIA MYOTONICA TYPE 1, OMIM:160900
Mode of pathogenicity for gene DMPK was changed from Other - please provide details in the comments to Other
Mode of inheritance for gene: DMPK was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Tag Q3_21_MOI tag was added to gene: DMPK.
Tag Q3_21_rating tag was added to gene: DMPK.
Tag nucleotide-repeat-expansion tag was added to gene: DMPK. Tag currently-ngs-unreportable tag was added to gene: DMPK.
Gene: dmpk has been classified as Green List (High Evidence).
Rebecca Foulger: Original DDG2P rating: confirm
gene: DMPK was added gene: DMPK was added to DDG2P. Sources: Expert Review Green,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 160900 Mode of pathogenicity for gene: DMPK was set to Other - please provide details in the comments