TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24441	73546;73547;73548	chr2:178572811;178572810;178572809	chr2:179437538;179437537;179437536
N2AB	22800	68623;68624;68625	chr2:178572811;178572810;178572809	chr2:179437538;179437537;179437536
N2A	21873	65842;65843;65844	chr2:178572811;178572810;178572809	chr2:179437538;179437537;179437536
N2B	15376	46351;46352;46353	chr2:178572811;178572810;178572809	chr2:179437538;179437537;179437536
Novex-1	15501	46726;46727;46728	chr2:178572811;178572810;178572809	chr2:179437538;179437537;179437536
Novex-2	15568	46927;46928;46929	chr2:178572811;178572810;178572809	chr2:179437538;179437537;179437536
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-132
• Domain position: 11
• Structural Position: 18
• Q(SASA): 0.6835
• 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
R/K	rs1559418326	None	0.997	N	0.581	0.307	0.40722173914	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
R/K	rs1559418326	None	0.997	N	0.581	0.307	0.40722173914	gnomAD-4.0.0	3.42177E-06	None	None	None	None	I	None	0	2.23664E-05	None	0	0	None	0	0	3.59846E-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
R/A	0.9596	likely_pathogenic	0.9539	pathogenic	0.127	Stabilizing	0.999	D	0.667	neutral	None	None	None	None	I
R/C	0.7615	likely_pathogenic	0.7542	pathogenic	-0.042	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
R/D	0.9866	likely_pathogenic	0.9852	pathogenic	-0.164	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
R/E	0.9274	likely_pathogenic	0.9216	pathogenic	-0.091	Destabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	I
R/F	0.9752	likely_pathogenic	0.9735	pathogenic	-0.049	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
R/G	0.9298	likely_pathogenic	0.9178	pathogenic	-0.078	Destabilizing	1.0	D	0.675	neutral	N	0.521522899	None	None	I
R/H	0.3897	ambiguous	0.3837	ambiguous	-0.664	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
R/I	0.9423	likely_pathogenic	0.9407	pathogenic	0.632	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
R/K	0.3167	likely_benign	0.2901	benign	0.02	Stabilizing	0.997	D	0.581	neutral	N	0.491306135	None	None	I
R/L	0.8574	likely_pathogenic	0.8445	pathogenic	0.632	Stabilizing	1.0	D	0.675	neutral	None	None	None	None	I
R/M	0.9118	likely_pathogenic	0.9043	pathogenic	0.091	Stabilizing	1.0	D	0.692	prob.neutral	N	0.492569318	None	None	I
R/N	0.97	likely_pathogenic	0.9681	pathogenic	0.176	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
R/P	0.9156	likely_pathogenic	0.9024	pathogenic	0.485	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
R/Q	0.4148	ambiguous	0.3878	ambiguous	0.136	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
R/S	0.9746	likely_pathogenic	0.9696	pathogenic	-0.066	Destabilizing	1.0	D	0.685	prob.neutral	N	0.502578816	None	None	I
R/T	0.9373	likely_pathogenic	0.9307	pathogenic	0.144	Stabilizing	1.0	D	0.682	prob.neutral	N	0.502404686	None	None	I
R/V	0.9511	likely_pathogenic	0.9487	pathogenic	0.485	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
R/W	0.7326	likely_pathogenic	0.721	pathogenic	-0.155	Destabilizing	1.0	D	0.761	deleterious	D	0.534146652	None	None	I
R/Y	0.9162	likely_pathogenic	0.9125	pathogenic	0.258	Stabilizing	1.0	D	0.735	prob.delet.	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.