TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25024	75295;75296;75297	chr2:178571062;178571061;178571060	chr2:179435789;179435788;179435787
N2AB	23383	70372;70373;70374	chr2:178571062;178571061;178571060	chr2:179435789;179435788;179435787
N2A	22456	67591;67592;67593	chr2:178571062;178571061;178571060	chr2:179435789;179435788;179435787
N2B	15959	48100;48101;48102	chr2:178571062;178571061;178571060	chr2:179435789;179435788;179435787
Novex-1	16084	48475;48476;48477	chr2:178571062;178571061;178571060	chr2:179435789;179435788;179435787
Novex-2	16151	48676;48677;48678	chr2:178571062;178571061;178571060	chr2:179435789;179435788;179435787
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-70
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.1948
• 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/S	rs1559397320	None	0.958	N	0.413	0.302	0.246773566709	gnomAD-4.0.0	1.59392E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8648E-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	0.0938	likely_benign	0.0963	benign	-1.015	Destabilizing	0.958	D	0.417	neutral	N	0.477764794	None	None	N
T/C	0.3713	ambiguous	0.35	ambiguous	-0.819	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
T/D	0.5366	ambiguous	0.5353	ambiguous	-0.926	Destabilizing	0.086	N	0.378	neutral	None	None	None	None	N
T/E	0.4028	ambiguous	0.3961	ambiguous	-0.802	Destabilizing	0.938	D	0.531	neutral	None	None	None	None	N
T/F	0.2308	likely_benign	0.2153	benign	-0.704	Destabilizing	0.998	D	0.779	deleterious	None	None	None	None	N
T/G	0.3454	ambiguous	0.3338	benign	-1.378	Destabilizing	0.968	D	0.616	neutral	None	None	None	None	N
T/H	0.2435	likely_benign	0.2267	benign	-1.526	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
T/I	0.1505	likely_benign	0.1453	benign	-0.096	Destabilizing	0.994	D	0.703	prob.neutral	N	0.486412074	None	None	N
T/K	0.2097	likely_benign	0.2056	benign	-0.72	Destabilizing	0.991	D	0.644	neutral	None	None	None	None	N
T/L	0.1107	likely_benign	0.1043	benign	-0.096	Destabilizing	0.984	D	0.58	neutral	None	None	None	None	N
T/M	0.0918	likely_benign	0.0884	benign	-0.107	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
T/N	0.1537	likely_benign	0.1488	benign	-1.076	Destabilizing	0.976	D	0.571	neutral	N	0.477524531	None	None	N
T/P	0.6821	likely_pathogenic	0.6757	pathogenic	-0.37	Destabilizing	0.994	D	0.703	prob.neutral	N	0.519355355	None	None	N
T/Q	0.2423	likely_benign	0.2322	benign	-1.018	Destabilizing	0.995	D	0.729	prob.delet.	None	None	None	None	N
T/R	0.1817	likely_benign	0.1688	benign	-0.731	Destabilizing	0.995	D	0.721	prob.delet.	None	None	None	None	N
T/S	0.1087	likely_benign	0.1073	benign	-1.335	Destabilizing	0.958	D	0.413	neutral	N	0.510515466	None	None	N
T/V	0.1319	likely_benign	0.13	benign	-0.37	Destabilizing	0.984	D	0.45	neutral	None	None	None	None	N
T/W	0.6	likely_pathogenic	0.5769	pathogenic	-0.744	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
T/Y	0.2668	likely_benign	0.2481	benign	-0.434	Destabilizing	0.998	D	0.775	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.