TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1322	4189;4190;4191	chr2:178779118;178779117;178779116	chr2:179643845;179643844;179643843
N2AB	1322	4189;4190;4191	chr2:178779118;178779117;178779116	chr2:179643845;179643844;179643843
N2A	1322	4189;4190;4191	chr2:178779118;178779117;178779116	chr2:179643845;179643844;179643843
N2B	1276	4051;4052;4053	chr2:178779118;178779117;178779116	chr2:179643845;179643844;179643843
Novex-1	1276	4051;4052;4053	chr2:178779118;178779117;178779116	chr2:179643845;179643844;179643843
Novex-2	1276	4051;4052;4053	chr2:178779118;178779117;178779116	chr2:179643845;179643844;179643843
Novex-3	1322	4189;4190;4191	chr2:178779118;178779117;178779116	chr2:179643845;179643844;179643843

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-5
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.2827
• 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
I/L	None	None	0.58	N	0.442	0.413	0.541285430251	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
I/A	0.8813	likely_pathogenic	0.9046	pathogenic	-2.022	Highly Destabilizing	0.91	D	0.673	neutral	None	None	None	None	I
I/C	0.9807	likely_pathogenic	0.9838	pathogenic	-1.049	Destabilizing	0.999	D	0.67	neutral	None	None	None	None	I
I/D	0.9987	likely_pathogenic	0.999	pathogenic	-1.774	Destabilizing	0.998	D	0.831	deleterious	None	None	None	None	I
I/E	0.9939	likely_pathogenic	0.9953	pathogenic	-1.637	Destabilizing	0.993	D	0.836	deleterious	None	None	None	None	I
I/F	0.7382	likely_pathogenic	0.7588	pathogenic	-1.235	Destabilizing	0.991	D	0.683	prob.neutral	D	0.56285611	None	None	I
I/G	0.9914	likely_pathogenic	0.9927	pathogenic	-2.452	Highly Destabilizing	0.993	D	0.834	deleterious	None	None	None	None	I
I/H	0.9946	likely_pathogenic	0.9962	pathogenic	-1.579	Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	I
I/K	0.9883	likely_pathogenic	0.9913	pathogenic	-1.329	Destabilizing	0.993	D	0.835	deleterious	None	None	None	None	I
I/L	0.3874	ambiguous	0.4032	ambiguous	-0.831	Destabilizing	0.58	D	0.442	neutral	N	0.514993144	None	None	I
I/M	0.3187	likely_benign	0.3324	benign	-0.644	Destabilizing	0.991	D	0.649	neutral	D	0.592142087	None	None	I
I/N	0.9761	likely_pathogenic	0.9825	pathogenic	-1.397	Destabilizing	0.997	D	0.829	deleterious	D	0.736640367	None	None	I
I/P	0.9921	likely_pathogenic	0.9934	pathogenic	-1.204	Destabilizing	0.998	D	0.83	deleterious	None	None	None	None	I
I/Q	0.9901	likely_pathogenic	0.9926	pathogenic	-1.413	Destabilizing	0.998	D	0.832	deleterious	None	None	None	None	I
I/R	0.984	likely_pathogenic	0.9884	pathogenic	-0.904	Destabilizing	0.998	D	0.834	deleterious	None	None	None	None	I
I/S	0.959	likely_pathogenic	0.9696	pathogenic	-2.051	Highly Destabilizing	0.991	D	0.809	deleterious	D	0.698951367	None	None	I
I/T	0.7788	likely_pathogenic	0.8579	pathogenic	-1.781	Destabilizing	0.939	D	0.717	prob.delet.	D	0.636722495	None	None	I
I/V	0.1603	likely_benign	0.1764	benign	-1.204	Destabilizing	0.02	N	0.188	neutral	N	0.441188942	None	None	I
I/W	0.9929	likely_pathogenic	0.9936	pathogenic	-1.429	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	I
I/Y	0.9718	likely_pathogenic	0.9761	pathogenic	-1.155	Destabilizing	0.998	D	0.686	prob.neutral	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.