TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26026	78301;78302;78303	chr2:178568056;178568055;178568054	chr2:179432783;179432782;179432781
N2AB	24385	73378;73379;73380	chr2:178568056;178568055;178568054	chr2:179432783;179432782;179432781
N2A	23458	70597;70598;70599	chr2:178568056;178568055;178568054	chr2:179432783;179432782;179432781
N2B	16961	51106;51107;51108	chr2:178568056;178568055;178568054	chr2:179432783;179432782;179432781
Novex-1	17086	51481;51482;51483	chr2:178568056;178568055;178568054	chr2:179432783;179432782;179432781
Novex-2	17153	51682;51683;51684	chr2:178568056;178568055;178568054	chr2:179432783;179432782;179432781
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Fn3-77
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.2973
• 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
H/N	None	None	0.904	N	0.61	0.388	0.328222422547	gnomAD-4.0.0	1.59222E-06	None	None	None	None	N	None	0	0	None	0	2.77963E-05	None	0	0	0	0	0
H/Q	rs1353297321	None	0.97	N	0.635	0.314	0.369682402691	gnomAD-4.0.0	6.84382E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99603E-07	0	0
H/Y	rs1164632947	0.378	0.014	N	0.479	0.343	0.229264304666	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
H/Y	rs1164632947	0.378	0.014	N	0.479	0.343	0.229264304666	gnomAD-4.0.0	1.59222E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85959E-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
H/A	0.9344	likely_pathogenic	0.9503	pathogenic	-1.956	Destabilizing	0.86	D	0.619	neutral	None	None	None	None	N
H/C	0.4932	ambiguous	0.531	ambiguous	-1.011	Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
H/D	0.9513	likely_pathogenic	0.9677	pathogenic	-1.916	Destabilizing	0.99	D	0.661	neutral	N	0.518209443	None	None	N
H/E	0.9314	likely_pathogenic	0.9481	pathogenic	-1.729	Destabilizing	0.926	D	0.594	neutral	None	None	None	None	N
H/F	0.5054	ambiguous	0.5246	ambiguous	0.027	Stabilizing	0.915	D	0.658	neutral	None	None	None	None	N
H/G	0.9671	likely_pathogenic	0.9778	pathogenic	-2.342	Highly Destabilizing	0.926	D	0.645	neutral	None	None	None	None	N
H/I	0.6322	likely_pathogenic	0.6767	pathogenic	-0.802	Destabilizing	0.956	D	0.739	prob.delet.	None	None	None	None	N
H/K	0.8728	likely_pathogenic	0.8898	pathogenic	-1.489	Destabilizing	0.978	D	0.659	neutral	None	None	None	None	N
H/L	0.4529	ambiguous	0.4994	ambiguous	-0.802	Destabilizing	0.698	D	0.685	prob.neutral	N	0.471341003	None	None	N
H/M	0.8624	likely_pathogenic	0.8814	pathogenic	-0.904	Destabilizing	0.998	D	0.721	prob.delet.	None	None	None	None	N
H/N	0.5377	ambiguous	0.6283	pathogenic	-2.042	Highly Destabilizing	0.904	D	0.61	neutral	N	0.504125425	None	None	N
H/P	0.9917	likely_pathogenic	0.9952	pathogenic	-1.18	Destabilizing	0.99	D	0.715	prob.delet.	N	0.503120296	None	None	N
H/Q	0.7396	likely_pathogenic	0.771	pathogenic	-1.618	Destabilizing	0.97	D	0.635	neutral	N	0.515707855	None	None	N
H/R	0.5308	ambiguous	0.5649	pathogenic	-1.787	Destabilizing	0.97	D	0.626	neutral	N	0.498063457	None	None	N
H/S	0.8283	likely_pathogenic	0.8675	pathogenic	-2.109	Highly Destabilizing	0.926	D	0.639	neutral	None	None	None	None	N
H/T	0.8322	likely_pathogenic	0.8699	pathogenic	-1.821	Destabilizing	0.978	D	0.656	neutral	None	None	None	None	N
H/V	0.6616	likely_pathogenic	0.6978	pathogenic	-1.18	Destabilizing	0.956	D	0.702	prob.neutral	None	None	None	None	N
H/W	0.5158	ambiguous	0.5462	ambiguous	0.518	Stabilizing	0.994	D	0.725	prob.delet.	None	None	None	None	N
H/Y	0.1818	likely_benign	0.1886	benign	0.267	Stabilizing	0.014	N	0.479	neutral	N	0.488908043	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.