TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33477	100654;100655;100656	chr2:178536318;178536317;178536316	chr2:179401045;179401044;179401043
N2AB	31836	95731;95732;95733	chr2:178536318;178536317;178536316	chr2:179401045;179401044;179401043
N2A	30909	92950;92951;92952	chr2:178536318;178536317;178536316	chr2:179401045;179401044;179401043
N2B	24412	73459;73460;73461	chr2:178536318;178536317;178536316	chr2:179401045;179401044;179401043
Novex-1	24537	73834;73835;73836	chr2:178536318;178536317;178536316	chr2:179401045;179401044;179401043
Novex-2	24604	74035;74036;74037	chr2:178536318;178536317;178536316	chr2:179401045;179401044;179401043
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-131
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.6787
• Predicted PPI site: I

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
E/Q	rs794729556	None	0.997	N	0.669	0.227	0.273070737957	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/Q	rs794729556	None	0.997	N	0.669	0.227	0.273070737957	gnomAD-4.0.0	6.57022E-06	None	None	None	None	I	None	2.41196E-05	0	None	0	0	None	0	0	0	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
E/A	0.1548	likely_benign	0.1587	benign	-0.57	Destabilizing	0.989	D	0.635	neutral	N	0.509264673	None	None	I
E/C	0.8439	likely_pathogenic	0.8318	pathogenic	-0.15	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
E/D	0.093	likely_benign	0.0763	benign	-0.462	Destabilizing	0.054	N	0.203	neutral	N	0.475210814	None	None	I
E/F	0.7716	likely_pathogenic	0.7602	pathogenic	-0.331	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
E/G	0.1729	likely_benign	0.1815	benign	-0.791	Destabilizing	0.978	D	0.637	neutral	N	0.47184931	None	None	I
E/H	0.5774	likely_pathogenic	0.5646	pathogenic	-0.126	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	I
E/I	0.3495	ambiguous	0.3334	benign	-0.01	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	I
E/K	0.1865	likely_benign	0.2247	benign	0.159	Stabilizing	0.978	D	0.605	neutral	N	0.488428041	None	None	I
E/L	0.4072	ambiguous	0.3945	ambiguous	-0.01	Destabilizing	0.998	D	0.747	deleterious	None	None	None	None	I
E/M	0.5288	ambiguous	0.5043	ambiguous	0.162	Stabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
E/N	0.2213	likely_benign	0.1965	benign	-0.215	Destabilizing	0.995	D	0.673	neutral	None	None	None	None	I
E/P	0.4249	ambiguous	0.4755	ambiguous	-0.177	Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	I
E/Q	0.197	likely_benign	0.1988	benign	-0.166	Destabilizing	0.997	D	0.669	neutral	N	0.507821878	None	None	I
E/R	0.3313	likely_benign	0.3914	ambiguous	0.419	Stabilizing	0.998	D	0.679	prob.neutral	None	None	None	None	I
E/S	0.1864	likely_benign	0.1775	benign	-0.39	Destabilizing	0.983	D	0.608	neutral	None	None	None	None	I
E/T	0.2246	likely_benign	0.2127	benign	-0.205	Destabilizing	0.998	D	0.655	neutral	None	None	None	None	I
E/V	0.2271	likely_benign	0.2168	benign	-0.177	Destabilizing	0.999	D	0.722	prob.delet.	N	0.4751939	None	None	I
E/W	0.9197	likely_pathogenic	0.9234	pathogenic	-0.116	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
E/Y	0.6628	likely_pathogenic	0.6537	pathogenic	-0.074	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I

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.