Gene Validity Classification Summary

Gene/Disease Pair:

MUTYH : Colorectal cancer Susceptibility

HGNC:7527 | OrphaNet: 247798 | OMIM:N/A
Mode of Inheritance: Autosomal dominant inheritance (HP:0000006)

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
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
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 LOD Score Examples 3 5 0-7 7
2 4
1.5 3
1 1.5
   
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 2.0 2
Theodoratou E et al. 2010 Dec 7 (PMID:21063410);
Aggregate Variant Analysis 0-6 12 5.0 5
Win AK et al. 2014 May (PMID:24444654);
Total Genetic Evidence Points (Maximum 12) 7
Experimental Evidence
Evidence Category Evidence Type Guidelines Scores PMIDs/Notes
Default Range Max Points Tally
Function Biochemical Function 0.5 0 - 2 2 1.5 1.5
Gu Y et al. 2002 Mar 29 (PMID:11801590); Banda DM et al. 2017 Jun (PMID:28087410); Tominaga Y et al. 2004 (PMID:15199168); Venesio T et al. 2012 (PMID:22876359);
Protein Interaction 0.5 0 - 2
Expression 0.5 0 - 2
Functional Alteration Patient cells 1 0 - 2 2 1.0 1
Grasso F et al. 2014 Jul 15 (PMID:24569162); Shinmura K et al. 2012 Dec 21 (PMID:23322991); Hirano S et al. 2003 Oct 3 (PMID:12917422);
Non-patient cells 0.5 0 - 1
Models & Rescue Animal model 2 0 - 4 4 2.0 2
Sieber OM et al. 2004 Dec 15 (PMID:15604247);
Cell culture model system 1 0 - 2
Rescue in animal model 2 0 - 4
Rescue in engineered equivalent 1 0 - 2
Total Experimental Evidence Points (Maximum 6) 4.5

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 7 4.5 11.5 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)
STRONG
10/09/2017
EXPERT CURATION (DATE)
MODERATE
10/09/2017