TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32952	99079;99080;99081	chr2:178539081;178539080;178539079	chr2:179403808;179403807;179403806
N2AB	31311	94156;94157;94158	chr2:178539081;178539080;178539079	chr2:179403808;179403807;179403806
N2A	30384	91375;91376;91377	chr2:178539081;178539080;178539079	chr2:179403808;179403807;179403806
N2B	23887	71884;71885;71886	chr2:178539081;178539080;178539079	chr2:179403808;179403807;179403806
Novex-1	24012	72259;72260;72261	chr2:178539081;178539080;178539079	chr2:179403808;179403807;179403806
Novex-2	24079	72460;72461;72462	chr2:178539081;178539080;178539079	chr2:179403808;179403807;179403806
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-128
• Domain position: 57
• Structural Position: 77
• Q(SASA): 0.0911
• 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
I/F	rs977201230	-1.39	0.998	N	0.687	0.413	0.441221003447	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	5.8E-05	None	0	0	None	0	None	0	0	0
I/F	rs977201230	-1.39	0.998	N	0.687	0.413	0.441221003447	gnomAD-4.0.0	4.77394E-06	None	None	None	None	N	None	0	6.85997E-05	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
I/A	0.9546	likely_pathogenic	0.9513	pathogenic	-1.93	Destabilizing	0.992	D	0.518	neutral	None	None	None	None	N
I/C	0.9593	likely_pathogenic	0.9554	pathogenic	-0.956	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
I/D	0.9966	likely_pathogenic	0.9966	pathogenic	-2.085	Highly Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
I/E	0.9887	likely_pathogenic	0.9878	pathogenic	-1.793	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
I/F	0.781	likely_pathogenic	0.7594	pathogenic	-1.054	Destabilizing	0.998	D	0.687	prob.neutral	N	0.515478569	None	None	N
I/G	0.9921	likely_pathogenic	0.992	pathogenic	-2.52	Highly Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
I/H	0.9879	likely_pathogenic	0.9856	pathogenic	-2.239	Highly Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
I/K	0.9816	likely_pathogenic	0.9774	pathogenic	-1.084	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
I/L	0.4205	ambiguous	0.4089	ambiguous	-0.202	Destabilizing	0.889	D	0.4	neutral	N	0.455238187	None	None	N
I/M	0.3728	ambiguous	0.3528	ambiguous	-0.251	Destabilizing	0.998	D	0.672	neutral	N	0.470937484	None	None	N
I/N	0.9435	likely_pathogenic	0.9387	pathogenic	-1.593	Destabilizing	0.999	D	0.795	deleterious	N	0.496986022	None	None	N
I/P	0.9935	likely_pathogenic	0.9942	pathogenic	-0.762	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
I/Q	0.9798	likely_pathogenic	0.9775	pathogenic	-1.284	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
I/R	0.9764	likely_pathogenic	0.9692	pathogenic	-1.243	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
I/S	0.9621	likely_pathogenic	0.959	pathogenic	-2.262	Highly Destabilizing	0.998	D	0.705	prob.neutral	N	0.493676358	None	None	N
I/T	0.9193	likely_pathogenic	0.9098	pathogenic	-1.806	Destabilizing	0.989	D	0.645	neutral	N	0.476840036	None	None	N
I/V	0.1677	likely_benign	0.1573	benign	-0.762	Destabilizing	0.333	N	0.234	neutral	N	0.440287377	None	None	N
I/W	0.9936	likely_pathogenic	0.992	pathogenic	-1.476	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
I/Y	0.972	likely_pathogenic	0.9656	pathogenic	-1.102	Destabilizing	1.0	D	0.729	prob.delet.	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.