TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18720	56383;56384;56385	chr2:178599743;178599742;178599741	chr2:179464470;179464469;179464468
N2AB	17079	51460;51461;51462	chr2:178599743;178599742;178599741	chr2:179464470;179464469;179464468
N2A	16152	48679;48680;48681	chr2:178599743;178599742;178599741	chr2:179464470;179464469;179464468
N2B	9655	29188;29189;29190	chr2:178599743;178599742;178599741	chr2:179464470;179464469;179464468
Novex-1	9780	29563;29564;29565	chr2:178599743;178599742;178599741	chr2:179464470;179464469;179464468
Novex-2	9847	29764;29765;29766	chr2:178599743;178599742;178599741	chr2:179464470;179464469;179464468
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-116
• Domain position: 33
• Structural Position: 50
• Q(SASA): 0.1723
• 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
K/T	rs1200935663	-1.425	0.83	N	0.726	0.377	0.32580497728	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
K/T	rs1200935663	-1.425	0.83	N	0.726	0.377	0.32580497728	gnomAD-4.0.0	3.18682E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72354E-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
K/A	0.87	likely_pathogenic	0.8332	pathogenic	-0.796	Destabilizing	0.648	D	0.62	neutral	None	None	None	None	N
K/C	0.8227	likely_pathogenic	0.7934	pathogenic	-0.903	Destabilizing	0.993	D	0.818	deleterious	None	None	None	None	N
K/D	0.9828	likely_pathogenic	0.9803	pathogenic	-0.337	Destabilizing	0.866	D	0.753	deleterious	None	None	None	None	N
K/E	0.7614	likely_pathogenic	0.7014	pathogenic	-0.174	Destabilizing	0.41	N	0.565	neutral	N	0.505420793	None	None	N
K/F	0.9017	likely_pathogenic	0.8712	pathogenic	-0.326	Destabilizing	0.98	D	0.82	deleterious	None	None	None	None	N
K/G	0.9506	likely_pathogenic	0.9356	pathogenic	-1.21	Destabilizing	0.866	D	0.732	prob.delet.	None	None	None	None	N
K/H	0.5191	ambiguous	0.4536	ambiguous	-1.527	Destabilizing	0.98	D	0.766	deleterious	None	None	None	None	N
K/I	0.6703	likely_pathogenic	0.6248	pathogenic	0.306	Stabilizing	0.908	D	0.824	deleterious	N	0.490163694	None	None	N
K/L	0.6523	likely_pathogenic	0.6011	pathogenic	0.306	Stabilizing	0.866	D	0.732	prob.delet.	None	None	None	None	N
K/M	0.5555	ambiguous	0.4896	ambiguous	0.092	Stabilizing	0.993	D	0.76	deleterious	None	None	None	None	N
K/N	0.9334	likely_pathogenic	0.9197	pathogenic	-0.753	Destabilizing	0.83	D	0.719	prob.delet.	N	0.491177652	None	None	N
K/P	0.9871	likely_pathogenic	0.9835	pathogenic	-0.032	Destabilizing	0.929	D	0.757	deleterious	None	None	None	None	N
K/Q	0.356	ambiguous	0.3028	benign	-0.733	Destabilizing	0.83	D	0.713	prob.delet.	N	0.504660325	None	None	N
K/R	0.097	likely_benign	0.0893	benign	-0.772	Destabilizing	0.01	N	0.383	neutral	N	0.492518778	None	None	N
K/S	0.9145	likely_pathogenic	0.8826	pathogenic	-1.445	Destabilizing	0.648	D	0.593	neutral	None	None	None	None	N
K/T	0.6925	likely_pathogenic	0.6196	pathogenic	-1.052	Destabilizing	0.83	D	0.726	prob.delet.	N	0.479567857	None	None	N
K/V	0.6444	likely_pathogenic	0.5945	pathogenic	-0.032	Destabilizing	0.866	D	0.762	deleterious	None	None	None	None	N
K/W	0.8806	likely_pathogenic	0.8338	pathogenic	-0.198	Destabilizing	0.993	D	0.805	deleterious	None	None	None	None	N
K/Y	0.8174	likely_pathogenic	0.777	pathogenic	0.109	Stabilizing	0.929	D	0.806	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.