|
|
Evidence Type |
Case Information Type |
Guidelines |
|
Points |
PMIDs/Notes |
Default |
Range |
Max |
Count |
Total |
Counted |
|
Autosomal Dominant or X-linked Disorder |
Variant is de novo |
2 |
0-3 |
12 |
|
|
|
|
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 |
|
|
|
|
Autosomal Recessive Disease |
Two variants in trans and at least one de novo or a predicted/proven null variant |
2 |
0-3 |
12 |
7 |
15
|
12
|
Varon R et al. 1998 May 1 (PMID:9590180); Nakanishi K et al. 2002 Dec (PMID:12447395);
|
Two variants (not predicted/proven null) with some evidence of gene impact in trans |
1 |
0-1.5 |
|
|
|
Segregation Evidence |
|
Summed LOD |
Family Count |
|
|
|
Candidate gene sequencing |
|
|
|
Exome/genome or all genes sequenced in linkage region |
|
|
|
Total Summed LOD Score |
|
|
|
|
Case-Control Study Type |
Case-Control Quality Criteria |
Guidelines |
|
Points |
PMIDs/Notes |
Points/Study |
Max |
Count |
Points |
Counted |
Single Variant Analysis |
1. Variant Detection Methodology
2. Power
3. Bias and confounding
4. Statistical Significance |
0-6 |
12 |
|
|
|
|
Aggregate Variant Analysis |
0-6 |
|
|
|
Total Genetic Evidence Points (Maximum 12) |
12
|
|
|
Evidence Category |
Evidence Type |
Guidelines |
|
Points |
PMIDs/Notes |
Default |
Range |
Max |
Count |
Total |
Counted |
Function |
Biochemical Function |
0.5 |
0 - 2 |
2 |
2 |
1
|
2
|
Waltes R et al. 2009 May (PMID:19409520); Stewart GS et al. 1999 Dec 10 (PMID:10612394);
|
Protein Interaction |
0.5 |
0 - 2 |
|
|
|
Expression |
0.5 |
0 - 2 |
2 |
1
|
Nakanishi K et al. 2002 Dec (PMID:12447395); Plisiecka-Hałasa J et al. 2002 Nov (PMID:12485469);
|
Functional Alteration |
Patient cells |
1 |
0 - 2 |
2 |
|
|
|
|
Non-patient cells |
0.5 |
0 - 1 |
|
|
|
Models |
Non-human model organism |
2 |
0 - 4 |
4 |
3 |
5
|
4
|
Williams BR et al. 2002 Apr 16 (PMID:11967151); Demuth I et al. 2004 Oct 15 (PMID:15333589); Dumon-Jones V et al. 2003 Nov 1 (PMID:14612522);
|
Cell culture model |
1 |
0 - 2 |
|
|
|
Rescue |
Rescue in human |
2 |
0 - 4 |
|
|
|
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
|
|