TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6180	18763;18764;18765	chr2:178729715;178729714;178729713	chr2:179594442;179594441;179594440
N2AB	5863	17812;17813;17814	chr2:178729715;178729714;178729713	chr2:179594442;179594441;179594440
N2A	4936	15031;15032;15033	chr2:178729715;178729714;178729713	chr2:179594442;179594441;179594440
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-45
• Domain position: 76
• Structural Position: 158
• Q(SASA): 0.0848
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
A/P	None	None	1.0	D	0.886	0.587	0.73903095977	gnomAD-4.0.0	1.36847E-06	None	None	None	None	N	None	5.97729E-05	0	None	0	0	None	0	0	0	0	0
A/S	None	None	1.0	D	0.582	0.544	0.629616166261	gnomAD-4.0.0	4.10542E-06	None	None	None	None	N	None	2.98864E-05	0	None	0	0	None	0	0	4.49756E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
A/C	0.9091	likely_pathogenic	0.9114	pathogenic	-1.657	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
A/D	0.9893	likely_pathogenic	0.9854	pathogenic	-2.607	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.656645135	None	None	N
A/E	0.9767	likely_pathogenic	0.9685	pathogenic	-2.418	Highly Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
A/F	0.9012	likely_pathogenic	0.9076	pathogenic	-0.848	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
A/G	0.3255	likely_benign	0.2959	benign	-1.806	Destabilizing	1.0	D	0.585	neutral	D	0.594950059	None	None	N
A/H	0.9949	likely_pathogenic	0.9937	pathogenic	-1.975	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
A/I	0.5441	ambiguous	0.6105	pathogenic	-0.136	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
A/K	0.996	likely_pathogenic	0.9946	pathogenic	-1.311	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
A/L	0.6061	likely_pathogenic	0.6319	pathogenic	-0.136	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
A/M	0.748	likely_pathogenic	0.7644	pathogenic	-0.6	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
A/N	0.9791	likely_pathogenic	0.9757	pathogenic	-1.647	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
A/P	0.9857	likely_pathogenic	0.9847	pathogenic	-0.501	Destabilizing	1.0	D	0.886	deleterious	D	0.640191805	None	None	N
A/Q	0.9814	likely_pathogenic	0.9764	pathogenic	-1.495	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
A/R	0.9884	likely_pathogenic	0.985	pathogenic	-1.344	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
A/S	0.4518	ambiguous	0.4387	ambiguous	-2.073	Highly Destabilizing	1.0	D	0.582	neutral	D	0.618661213	None	None	N
A/T	0.5609	ambiguous	0.5595	ambiguous	-1.761	Destabilizing	1.0	D	0.791	deleterious	D	0.618459409	None	None	N
A/V	0.3181	likely_benign	0.3481	ambiguous	-0.501	Destabilizing	1.0	D	0.66	neutral	N	0.505315792	None	None	N
A/W	0.9953	likely_pathogenic	0.9948	pathogenic	-1.499	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
A/Y	0.9783	likely_pathogenic	0.9759	pathogenic	-1.014	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.