TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16217	48874;48875;48876	chr2:178614958;178614957;178614956	chr2:179479685;179479684;179479683
N2AB	14576	43951;43952;43953	chr2:178614958;178614957;178614956	chr2:179479685;179479684;179479683
N2A	13649	41170;41171;41172	chr2:178614958;178614957;178614956	chr2:179479685;179479684;179479683
N2B	7152	21679;21680;21681	chr2:178614958;178614957;178614956	chr2:179479685;179479684;179479683
Novex-1	7277	22054;22055;22056	chr2:178614958;178614957;178614956	chr2:179479685;179479684;179479683
Novex-2	7344	22255;22256;22257	chr2:178614958;178614957;178614956	chr2:179479685;179479684;179479683
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-5
• Domain position: 63
• Structural Position: 94
• Q(SASA): 0.5876
• 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
T/R	None	None	1.0	N	0.818	0.362	0.604264793904	gnomAD-4.0.0	1.63013E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.92401E-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
T/A	0.0874	likely_benign	0.079	benign	-0.563	Destabilizing	0.999	D	0.52	neutral	D	0.535967831	None	None	N
T/C	0.3742	ambiguous	0.368	ambiguous	-0.277	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
T/D	0.3633	ambiguous	0.3428	ambiguous	-0.046	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
T/E	0.247	likely_benign	0.2329	benign	-0.109	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
T/F	0.3079	likely_benign	0.2845	benign	-0.934	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
T/G	0.2025	likely_benign	0.1948	benign	-0.732	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
T/H	0.1998	likely_benign	0.1891	benign	-1.026	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
T/I	0.1808	likely_benign	0.1702	benign	-0.226	Destabilizing	1.0	D	0.821	deleterious	D	0.580363706	None	None	N
T/K	0.0968	likely_benign	0.0946	benign	-0.528	Destabilizing	1.0	D	0.817	deleterious	N	0.485140807	None	None	N
T/L	0.1175	likely_benign	0.1036	benign	-0.226	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
T/M	0.1168	likely_benign	0.1048	benign	0.099	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
T/N	0.1262	likely_benign	0.1225	benign	-0.295	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
T/P	0.1197	likely_benign	0.0984	benign	-0.308	Destabilizing	1.0	D	0.825	deleterious	D	0.529468846	None	None	N
T/Q	0.1643	likely_benign	0.1544	benign	-0.557	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
T/R	0.1163	likely_benign	0.1059	benign	-0.202	Destabilizing	1.0	D	0.818	deleterious	N	0.484833065	None	None	N
T/S	0.105	likely_benign	0.1021	benign	-0.535	Destabilizing	0.999	D	0.51	neutral	N	0.468153923	None	None	N
T/V	0.1312	likely_benign	0.1256	benign	-0.308	Destabilizing	0.999	D	0.589	neutral	None	None	None	None	N
T/W	0.6345	likely_pathogenic	0.5979	pathogenic	-0.886	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
T/Y	0.3622	ambiguous	0.3298	benign	-0.636	Destabilizing	1.0	D	0.817	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.