TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19669	59230;59231;59232	chr2:178593203;178593202;178593201	chr2:179457930;179457929;179457928
N2AB	18028	54307;54308;54309	chr2:178593203;178593202;178593201	chr2:179457930;179457929;179457928
N2A	17101	51526;51527;51528	chr2:178593203;178593202;178593201	chr2:179457930;179457929;179457928
N2B	10604	32035;32036;32037	chr2:178593203;178593202;178593201	chr2:179457930;179457929;179457928
Novex-1	10729	32410;32411;32412	chr2:178593203;178593202;178593201	chr2:179457930;179457929;179457928
Novex-2	10796	32611;32612;32613	chr2:178593203;178593202;178593201	chr2:179457930;179457929;179457928
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Fn3-30
• Domain position: 91
• Structural Position: 124
• Q(SASA): 0.294
• 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
S/P	None	None	0.999	D	0.849	0.421	0.532600205719	gnomAD-4.0.0	1.5921E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85936E-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
S/A	0.4576	ambiguous	0.4543	ambiguous	-0.647	Destabilizing	0.994	D	0.632	neutral	N	0.509727932	None	None	N
S/C	0.4424	ambiguous	0.4554	ambiguous	-0.424	Destabilizing	1.0	D	0.805	deleterious	N	0.520554486	None	None	N
S/D	0.9908	likely_pathogenic	0.9916	pathogenic	-1.149	Destabilizing	0.998	D	0.675	prob.neutral	None	None	None	None	N
S/E	0.9954	likely_pathogenic	0.9955	pathogenic	-0.975	Destabilizing	0.998	D	0.691	prob.delet.	None	None	None	None	N
S/F	0.9907	likely_pathogenic	0.9892	pathogenic	-0.354	Destabilizing	0.999	D	0.86	deleterious	D	0.531821886	None	None	N
S/G	0.478	ambiguous	0.4886	ambiguous	-1.046	Destabilizing	0.998	D	0.708	prob.delet.	None	None	None	None	N
S/H	0.9917	likely_pathogenic	0.9912	pathogenic	-1.415	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
S/I	0.9714	likely_pathogenic	0.9702	pathogenic	0.362	Stabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
S/K	0.9992	likely_pathogenic	0.9992	pathogenic	-0.406	Destabilizing	0.998	D	0.677	prob.neutral	None	None	None	None	N
S/L	0.8751	likely_pathogenic	0.8622	pathogenic	0.362	Stabilizing	0.999	D	0.786	deleterious	None	None	None	None	N
S/M	0.9228	likely_pathogenic	0.9222	pathogenic	0.252	Stabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
S/N	0.9623	likely_pathogenic	0.9625	pathogenic	-0.961	Destabilizing	0.998	D	0.711	prob.delet.	None	None	None	None	N
S/P	0.9945	likely_pathogenic	0.9933	pathogenic	0.062	Stabilizing	0.999	D	0.849	deleterious	D	0.543178191	None	None	N
S/Q	0.9931	likely_pathogenic	0.9931	pathogenic	-0.719	Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
S/R	0.9984	likely_pathogenic	0.9984	pathogenic	-0.75	Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
S/T	0.2488	likely_benign	0.2452	benign	-0.656	Destabilizing	0.997	D	0.708	prob.delet.	N	0.476241673	None	None	N
S/V	0.916	likely_pathogenic	0.9107	pathogenic	0.062	Stabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
S/W	0.9944	likely_pathogenic	0.993	pathogenic	-0.641	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
S/Y	0.991	likely_pathogenic	0.9895	pathogenic	-0.2	Destabilizing	0.999	D	0.887	deleterious	D	0.542924702	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.