Assertion criteria |
Genetic Evidence (0-12 points) |
Experimental Evidence
(0-6 points) |
Total Points
(0-18)
|
Replication Over Time (Y/N) |
Description |
Case-level, family segregation, or case-control data that support the gene-disease association
|
Gene-level experimental evidence that support the gene-disease association |
Sum of Genetic & Experimental
Evidence
|
> 2 pubs w/ convincing evidence over time (>3 yrs) |
Assigned Points |
=$inputThisData["summary"]["GeneticEvidenceTotal"]?>
1.5
|
=$inputThisData["summary"]["ExperimentalEvidenceTotal"]?>
0.5
|
=$inputThisData["summary"]["EvidencePointsTotal"]?>
2
|
NO
|
CALCULATED CLASSIFICATION |
LIMITED |
1-6 |
MODERATE |
7-11 |
STRONG |
12-18 |
DEFINITIVE |
12-18 AND replication over time |
Valid contradictory evidence (Y/N)*
|
|
CALCULATED CLASSIFICATION (DATE) |
Limited
07/01/2019
|
EXPERT CURATION (DATE) |
Limited
06/28/2019
|
EVIDENCE SUMMARY |
The relationship between DMGDH and dimethylglycine dehydrogenase deficiency was evaluated using
the ClinGen Clinical Validity Framework as of 4/23/19. A human with this disease was first reported in 1999 (Moolenaar et al; PMID: 10102904) with the variant being identified in 2001 (Binzak et al; PMID: 11231903). Only this one missense variant with functional evidence to support pathogenicity has been reported in humans.
This gene-disease relationship is also supported by biochemical assays.
In summary, there is limited evidence to support this gene-disease relationship mostly due to the lack of variants published in humans. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Aminoacidopathy Working Group on 06/28/19 (SOP Version 6).
|