TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26222	78889;78890;78891	chr2:178567468;178567467;178567466	chr2:179432195;179432194;179432193
N2AB	24581	73966;73967;73968	chr2:178567468;178567467;178567466	chr2:179432195;179432194;179432193
N2A	23654	71185;71186;71187	chr2:178567468;178567467;178567466	chr2:179432195;179432194;179432193
N2B	17157	51694;51695;51696	chr2:178567468;178567467;178567466	chr2:179432195;179432194;179432193
Novex-1	17282	52069;52070;52071	chr2:178567468;178567467;178567466	chr2:179432195;179432194;179432193
Novex-2	17349	52270;52271;52272	chr2:178567468;178567467;178567466	chr2:179432195;179432194;179432193
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-137
• Domain position: 30
• Structural Position: 43
• Q(SASA): 0.3094
• 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
L/R	rs1470470841	None	0.939	N	0.516	0.542	0.74021432234	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
L/R	rs1470470841	None	0.939	N	0.516	0.542	0.74021432234	gnomAD-4.0.0	1.31524E-05	None	None	None	None	N	None	4.82649E-05	0	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
L/A	0.2638	likely_benign	0.2609	benign	-1.093	Destabilizing	0.543	D	0.359	neutral	None	None	None	None	N
L/C	0.5918	likely_pathogenic	0.5659	pathogenic	-0.676	Destabilizing	0.996	D	0.451	neutral	None	None	None	None	N
L/D	0.776	likely_pathogenic	0.7798	pathogenic	-0.197	Destabilizing	0.984	D	0.521	neutral	None	None	None	None	N
L/E	0.4777	ambiguous	0.48	ambiguous	-0.226	Destabilizing	0.984	D	0.519	neutral	None	None	None	None	N
L/F	0.1915	likely_benign	0.1934	benign	-0.774	Destabilizing	0.02	N	0.183	neutral	None	None	None	None	N
L/G	0.6803	likely_pathogenic	0.6775	pathogenic	-1.352	Destabilizing	0.953	D	0.497	neutral	None	None	None	None	N
L/H	0.3448	ambiguous	0.3318	benign	-0.546	Destabilizing	0.996	D	0.509	neutral	None	None	None	None	N
L/I	0.0814	likely_benign	0.0855	benign	-0.491	Destabilizing	0.003	N	0.089	neutral	N	0.439359949	None	None	N
L/K	0.3439	ambiguous	0.34	benign	-0.604	Destabilizing	0.953	D	0.505	neutral	None	None	None	None	N
L/M	0.118	likely_benign	0.1237	benign	-0.477	Destabilizing	0.373	N	0.286	neutral	None	None	None	None	N
L/N	0.4558	ambiguous	0.458	ambiguous	-0.401	Destabilizing	0.984	D	0.522	neutral	None	None	None	None	N
L/P	0.2089	likely_benign	0.201	benign	-0.659	Destabilizing	0.979	D	0.523	neutral	N	0.465890403	None	None	N
L/Q	0.2346	likely_benign	0.2386	benign	-0.553	Destabilizing	0.939	D	0.516	neutral	N	0.491882138	None	None	N
L/R	0.2839	likely_benign	0.278	benign	-0.089	Destabilizing	0.939	D	0.516	neutral	N	0.48472688	None	None	N
L/S	0.3303	likely_benign	0.3352	benign	-0.985	Destabilizing	0.953	D	0.481	neutral	None	None	None	None	N
L/T	0.2696	likely_benign	0.2587	benign	-0.894	Destabilizing	0.742	D	0.405	neutral	None	None	None	None	N
L/V	0.0879	likely_benign	0.0911	benign	-0.659	Destabilizing	0.028	N	0.117	neutral	N	0.443514975	None	None	N
L/W	0.396	ambiguous	0.3852	ambiguous	-0.811	Destabilizing	0.996	D	0.531	neutral	None	None	None	None	N
L/Y	0.436	ambiguous	0.4173	ambiguous	-0.578	Destabilizing	0.835	D	0.463	neutral	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.