Gene Validity Curation

Gene Validity Classification Summary

Gene/Disease Pair:

SLC2A10 : Familial thoracic aortic aneurysm and aortic dissection

HGNC:13444 | OrphaNet: 91387 | OMIM: 606145
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
0.0
0
Proband with predicted or proven null variant 1.5 0-2 10 0.0 0
Proband with other variant type with some evidence of gene impact 0.5 0-1.5 7 0.0 0
Autosomal Recessive Disease Two variants in trans and at least one de novo or a predicted/proven null variant 2 0-3 12 0.0 0
Two variants (not predicted/proven null) with some evidence of gene impact in trans 1 0-1.5 0.0
Segregation Evidence Evidence of segregation in one or more families LOD Score Examples 3 5 0-7 7 0.0 0
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 0.0 0
Aggregate Variant Analysis 0-6 12 0.0 0
Total Genetic Evidence Points (Maximum 12)
No probands with isolated TAA were noted. But definitive evidence for Arterial Tortuosity syndrome.
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
Lee YC et al. 2010 Oct 1 (PMID:20639396); Coucke PJ et al. 2003 Oct (PMID:14569121); (Biochemical Function PMID 20639396: GLUT10 acts as a mitochondrial DHA transporter. Lack/reduced GLUT10 results in increased oxidative stress. Protein Interaction PMID 14569121: Disruption of SLC2A10 leads to TGF-beta signaling activation Expression: PMID 20639396: GLUT10 mRNA is highly expressed in aortic smooth muscle cells in humans and mice. In A10 rat aortic smooth muscle cells, Glut10 localized mainly to mitochondria PMID 14569121: qPCR of samples derived from individuals with ATS homozygous for premature stop codon mutations demonstrated a near-absence of SLC2A10 mRNA in vascular smooth muscle cells as well as in fibroblasts. )
Protein Interaction 0.5 0 - 2
Expression 0.5 0 - 2
Functional Alteration Patient cells 1 0 - 2 2 0.0
Non-patient cells 0.5 0 - 1
Models & Rescue Animal model 2 0 - 4 4 0.0 0
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) 1.5

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 1.5 1.5 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)
LIMITED
03/08/2016
EXPERT CURATION (DATE)
LIMITED
04/17/2016
Assertion made by the Aortopathy working group. Though experimental data may be available supporting a potential role for SLC2A10 in HTAAD, no probands with isolated TAAD have been reported to date. ATS patients should, however, be screened for TAA.Genes predictive of thoracic aortic enlargement without evidence of progression to aortic dissection so far. SLC2A10 may be predictive of thoracic aortic enlargement without evidence of progression to aortic dissection so far