TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24451	73576;73577;73578	chr2:178572781;178572780;178572779	chr2:179437508;179437507;179437506
N2AB	22810	68653;68654;68655	chr2:178572781;178572780;178572779	chr2:179437508;179437507;179437506
N2A	21883	65872;65873;65874	chr2:178572781;178572780;178572779	chr2:179437508;179437507;179437506
N2B	15386	46381;46382;46383	chr2:178572781;178572780;178572779	chr2:179437508;179437507;179437506
Novex-1	15511	46756;46757;46758	chr2:178572781;178572780;178572779	chr2:179437508;179437507;179437506
Novex-2	15578	46957;46958;46959	chr2:178572781;178572780;178572779	chr2:179437508;179437507;179437506
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-132
• Domain position: 21
• Structural Position: 34
• Q(SASA): 0.3383
• 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
P/R	None	None	0.142	N	0.544	0.394	0.509878532422	gnomAD-4.0.0	1.59192E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02517E-05

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
P/A	0.1958	likely_benign	0.2175	benign	-0.938	Destabilizing	0.958	D	0.632	neutral	D	0.532710041	None	None	I
P/C	0.8429	likely_pathogenic	0.8606	pathogenic	-0.741	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
P/D	0.9109	likely_pathogenic	0.9171	pathogenic	-0.576	Destabilizing	0.995	D	0.785	deleterious	None	None	None	None	I
P/E	0.7958	likely_pathogenic	0.8133	pathogenic	-0.556	Destabilizing	0.991	D	0.717	prob.delet.	None	None	None	None	I
P/F	0.9223	likely_pathogenic	0.9344	pathogenic	-0.615	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
P/G	0.6665	likely_pathogenic	0.6851	pathogenic	-1.226	Destabilizing	0.991	D	0.706	prob.neutral	None	None	None	None	I
P/H	0.6432	likely_pathogenic	0.6661	pathogenic	-0.555	Destabilizing	0.998	D	0.769	deleterious	N	0.488477487	None	None	I
P/I	0.7349	likely_pathogenic	0.7564	pathogenic	-0.257	Destabilizing	0.995	D	0.791	deleterious	None	None	None	None	I
P/K	0.779	likely_pathogenic	0.7883	pathogenic	-0.748	Destabilizing	0.938	D	0.705	prob.neutral	None	None	None	None	I
P/L	0.3663	ambiguous	0.4031	ambiguous	-0.257	Destabilizing	0.988	D	0.757	deleterious	N	0.491693491	None	None	I
P/M	0.6556	likely_pathogenic	0.6814	pathogenic	-0.418	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
P/N	0.7203	likely_pathogenic	0.7422	pathogenic	-0.728	Destabilizing	0.991	D	0.759	deleterious	None	None	None	None	I
P/Q	0.5535	ambiguous	0.5797	pathogenic	-0.807	Destabilizing	0.991	D	0.784	deleterious	None	None	None	None	I
P/R	0.6605	likely_pathogenic	0.6792	pathogenic	-0.321	Destabilizing	0.142	N	0.544	neutral	N	0.512604127	None	None	I
P/S	0.34	ambiguous	0.3824	ambiguous	-1.224	Destabilizing	0.988	D	0.705	prob.neutral	N	0.48218361	None	None	I
P/T	0.2072	likely_benign	0.2261	benign	-1.083	Destabilizing	0.988	D	0.735	prob.delet.	N	0.448648649	None	None	I
P/V	0.5385	ambiguous	0.5645	pathogenic	-0.449	Destabilizing	0.995	D	0.761	deleterious	None	None	None	None	I
P/W	0.9621	likely_pathogenic	0.9667	pathogenic	-0.803	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	I
P/Y	0.8961	likely_pathogenic	0.9104	pathogenic	-0.47	Destabilizing	1.0	D	0.785	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.