TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33748	101467;101468;101469	chr2:178535373;178535372;178535371	chr2:179400100;179400099;179400098
N2AB	32107	96544;96545;96546	chr2:178535373;178535372;178535371	chr2:179400100;179400099;179400098
N2A	31180	93763;93764;93765	chr2:178535373;178535372;178535371	chr2:179400100;179400099;179400098
N2B	24683	74272;74273;74274	chr2:178535373;178535372;178535371	chr2:179400100;179400099;179400098
Novex-1	24808	74647;74648;74649	chr2:178535373;178535372;178535371	chr2:179400100;179400099;179400098
Novex-2	24875	74848;74849;74850	chr2:178535373;178535372;178535371	chr2:179400100;179400099;179400098
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-132
• Domain position: 60
• Structural Position: 92
• Q(SASA): 0.3463
• 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
T/I	rs750315507	0.114	1.0	N	0.846	0.484	0.545869088564	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.77E-05	0
T/I	rs750315507	0.114	1.0	N	0.846	0.484	0.545869088564	gnomAD-4.0.0	1.36836E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79884E-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
T/A	0.2318	likely_benign	0.2034	benign	-0.664	Destabilizing	0.988	D	0.562	neutral	N	0.503170993	None	None	N
T/C	0.7107	likely_pathogenic	0.6643	pathogenic	-0.458	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
T/D	0.8737	likely_pathogenic	0.8619	pathogenic	0.242	Stabilizing	0.999	D	0.836	deleterious	None	None	None	None	N
T/E	0.7744	likely_pathogenic	0.7438	pathogenic	0.25	Stabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
T/F	0.8313	likely_pathogenic	0.8202	pathogenic	-0.818	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
T/G	0.686	likely_pathogenic	0.6761	pathogenic	-0.91	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
T/H	0.6573	likely_pathogenic	0.6134	pathogenic	-1.109	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
T/I	0.4984	ambiguous	0.4609	ambiguous	-0.109	Destabilizing	1.0	D	0.846	deleterious	N	0.472933083	None	None	N
T/K	0.585	likely_pathogenic	0.551	ambiguous	-0.481	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
T/L	0.3323	likely_benign	0.3076	benign	-0.109	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
T/M	0.2249	likely_benign	0.2024	benign	-0.071	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
T/N	0.407	ambiguous	0.3578	ambiguous	-0.483	Destabilizing	0.999	D	0.732	prob.delet.	N	0.477706023	None	None	N
T/P	0.4329	ambiguous	0.4393	ambiguous	-0.262	Destabilizing	0.999	D	0.848	deleterious	D	0.523527623	None	None	N
T/Q	0.5305	ambiguous	0.4807	ambiguous	-0.553	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
T/R	0.5253	ambiguous	0.4904	ambiguous	-0.32	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
T/S	0.3076	likely_benign	0.2773	benign	-0.78	Destabilizing	0.988	D	0.528	neutral	N	0.476553934	None	None	N
T/V	0.3267	likely_benign	0.2943	benign	-0.262	Destabilizing	0.999	D	0.601	neutral	None	None	None	None	N
T/W	0.9433	likely_pathogenic	0.9417	pathogenic	-0.799	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
T/Y	0.8337	likely_pathogenic	0.8256	pathogenic	-0.527	Destabilizing	1.0	D	0.879	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.