TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30262	91009;91010;91011	chr2:178552116;178552115;178552114	chr2:179416843;179416842;179416841
N2AB	28621	86086;86087;86088	chr2:178552116;178552115;178552114	chr2:179416843;179416842;179416841
N2A	27694	83305;83306;83307	chr2:178552116;178552115;178552114	chr2:179416843;179416842;179416841
N2B	21197	63814;63815;63816	chr2:178552116;178552115;178552114	chr2:179416843;179416842;179416841
Novex-1	21322	64189;64190;64191	chr2:178552116;178552115;178552114	chr2:179416843;179416842;179416841
Novex-2	21389	64390;64391;64392	chr2:178552116;178552115;178552114	chr2:179416843;179416842;179416841
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: Fn3-108
• Domain position: 39
• Structural Position: 40
• Q(SASA): 0.0636
• 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/L	None	None	0.437	N	0.313	0.123	0.533035250729	gnomAD-4.0.0	1.59129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85824E-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
I/A	0.8188	likely_pathogenic	0.8417	pathogenic	-2.695	Highly Destabilizing	0.702	D	0.643	neutral	None	None	None	None	N
I/C	0.9641	likely_pathogenic	0.9669	pathogenic	-2.126	Highly Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	N
I/D	0.9993	likely_pathogenic	0.9993	pathogenic	-3.418	Highly Destabilizing	0.996	D	0.857	deleterious	None	None	None	None	N
I/E	0.997	likely_pathogenic	0.9971	pathogenic	-3.08	Highly Destabilizing	0.988	D	0.833	deleterious	None	None	None	None	N
I/F	0.8223	likely_pathogenic	0.7979	pathogenic	-1.606	Destabilizing	0.968	D	0.651	neutral	N	0.515225341	None	None	N
I/G	0.9932	likely_pathogenic	0.9939	pathogenic	-3.328	Highly Destabilizing	0.988	D	0.8	deleterious	None	None	None	None	N
I/H	0.9983	likely_pathogenic	0.9981	pathogenic	-3.145	Highly Destabilizing	0.999	D	0.866	deleterious	None	None	None	None	N
I/K	0.9962	likely_pathogenic	0.996	pathogenic	-2.014	Highly Destabilizing	0.988	D	0.837	deleterious	None	None	None	None	N
I/L	0.2105	likely_benign	0.2051	benign	-0.781	Destabilizing	0.437	N	0.313	neutral	N	0.477984547	None	None	N
I/M	0.3296	likely_benign	0.3232	benign	-1.121	Destabilizing	0.994	D	0.633	neutral	N	0.496867597	None	None	N
I/N	0.9929	likely_pathogenic	0.992	pathogenic	-2.765	Highly Destabilizing	0.995	D	0.865	deleterious	N	0.515478831	None	None	N
I/P	0.9955	likely_pathogenic	0.9964	pathogenic	-1.411	Destabilizing	0.996	D	0.859	deleterious	None	None	None	None	N
I/Q	0.9963	likely_pathogenic	0.996	pathogenic	-2.368	Highly Destabilizing	0.996	D	0.875	deleterious	None	None	None	None	N
I/R	0.994	likely_pathogenic	0.9933	pathogenic	-2.181	Highly Destabilizing	0.988	D	0.866	deleterious	None	None	None	None	N
I/S	0.9721	likely_pathogenic	0.9723	pathogenic	-3.33	Highly Destabilizing	0.984	D	0.757	deleterious	N	0.515478831	None	None	N
I/T	0.7864	likely_pathogenic	0.8124	pathogenic	-2.815	Highly Destabilizing	0.896	D	0.605	neutral	N	0.515225341	None	None	N
I/V	0.0724	likely_benign	0.0732	benign	-1.411	Destabilizing	0.004	N	0.227	neutral	N	0.343622048	None	None	N
I/W	0.9974	likely_pathogenic	0.9974	pathogenic	-2.013	Highly Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	N
I/Y	0.9925	likely_pathogenic	0.9905	pathogenic	-1.81	Destabilizing	0.988	D	0.757	deleterious	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.