| Gene/Disease Pair: | DES : Myofibrillar myopathy |
| MONDO:0011076 | ORPHA:98909 | OMIM:601419 | |
| Mode of Inheritance: | Autosomal dominant inheritance (HP:0000006) |
| SOP: | Gene Clinical Validity Standard Operating Procedures (SOP), Version 5 |
|
Genetic Evidence
|
Case-Level Data
|
Evidence Type | Case Information Type | Guidelines | Scores | PMIDs/Notes | ||||||
| Default | Range | Max | Points | Tally | ||||||||
|
Variant Evidence
|
Autosomal Dominant or X-linked Disorder | Variant is de novo | 2 | 0-3 | 12 |
5.00
|
5 |
Sugawara M et al. 2000 Oct 10 (PMID:11061256); Dalakas MC et al. 2000 Mar 16 (PMID:10717012);
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| Proband with predicted or proven null variant | 1.5 | 0-2 | 10 | |||||||||
| Proband with other variant type with some evidence of gene impact | 0.5 | 0-1.5 | 7 |
5.50
|
5.5 |
Goldfarb LG et al. 1998 Aug (PMID:9697706); Sjöberg G et al. 1999 Nov (PMID:10545598); Sugawara M et al. 2000 Oct 10 (PMID:11061256); Clemen CS et al. 2009 Mar (PMID:19105189); Dalakas MC et al. 2000 Mar 16 (PMID:10717012); Bär H et al. 2007 Apr (PMID:17221859);
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| Autosomal Recessive Disease | Two variants in trans and at least one de novo or a predicted/proven null variant | 2 | 0-3 | 12 |
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| Two variants (not predicted/proven null) with some evidence of gene impact in trans | 1 | 0-1.5 | ||||||||||
| Segregation Evidence | Evidence of segregation in one or more families | Sequencing Method | 0-3 | 3 |
1.50
|
1.5 | ||||||
| Total LOD Score | Canditate Gene Sequencing | Exome/Genome or all genes sequenced in linkage region | ||||||||||
| 2-2.99 | 0.5 | 1 | ||||||||||
| 3-4.99 | 1 | 2 | ||||||||||
| ≥5 | 1.5 | 3 |
Sjöberg G et al. 1999 Nov (PMID:10545598);
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Case-Control Data
|
Case-Control Study Type | Case-Control Quality Criteria | Guidelines | Scores | PMIDs/Notes | |||||||
| Points/Study | Max | Points | Tally | |||||||||
| Single Variant Analysis | 1. Variant Detection Methodology 2. Power 3. Bias and confounding 4. Statistical Significance |
0-6 | 12 |
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| Aggregate Variant Analysis | 0-6 |
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| Total Genetic Evidence Points (Maximum 12) | 12 |
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|
Experimental Evidence
|
Evidence Category | Evidence Type | Guidelines | Scores | PMIDs/Notes | |||||||
| Default | Range | Max | Points | Tally | ||||||||
| Function | Biochemical Function | 0.5 | 0 - 2 | 2 |
0.50
|
1 |
Tidball JG et al. 1992 Apr (PMID:1544366);
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| Protein Interaction | 0.5 | 0 - 2 | ||||||||||
| Expression | 0.5 | 0 - 2 | 0.50 |
Li ZL et al. 1989 May 30 (PMID:2673923);
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| Functional Alteration | Patient cells | 1 | 0 - 2 | 2 |
|
1 | ||||||
| Non-patient cells | 0.5 | 0 - 1 | 1.00 |
Bär H et al. 2005 Oct 18 (PMID:16217025);
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| Models | Non-human model organism | 2 | 0 - 4 | 4 | 4.00 | 4 |
Hnia K et al. 2015 Jun (PMID:25358400);
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| Cell culture model | 1 | 0 - 2 | ||||||||||
| Rescue | Rescue in human | 2 | 0 - 4 |
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| Rescue in non-human model organism | 2 | 0 - 4 | ||||||||||
| Rescue in cell culture model | 1 | 0 - 2 | ||||||||||
| Rescue in patient cells | 1 | 0 - 2 | ||||||||||
| Total Experimental Evidence Points (Maximum 6) | 6 |
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| 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 | 12 | 6 | 18 | YES | ||
| CALCULATED CLASSIFICATION | LIMITED | 1-6 | ||||
| MODERATE | 7-11 | |||||
| STRONG | 12-18 | |||||
| DEFINITIVE | 12-18 AND replication over time | |||||
| Valid contradictory evidence (Y/N)*
|
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| CALCULATED CLASSIFICATION (DATE) |
DEFINITIVE
08/25/2017
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| EXPERT CURATION (DATE) |
DEFINITIVE
09/25/2017
Approved by Jonathan Berg, MD, PhD
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