TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4788	14587;14588;14589	chr2:178738091;178738090;178738089	chr2:179602818;179602817;179602816
N2AB	4471	13636;13637;13638	chr2:178738091;178738090;178738089	chr2:179602818;179602817;179602816
N2A	3544	10855;10856;10857	chr2:178738091;178738090;178738089	chr2:179602818;179602817;179602816
N2B	4425	13498;13499;13500	chr2:178738091;178738090;178738089	chr2:179602818;179602817;179602816
Novex-1	4550	13873;13874;13875	chr2:178738091;178738090;178738089	chr2:179602818;179602817;179602816
Novex-2	4617	14074;14075;14076	chr2:178738091;178738090;178738089	chr2:179602818;179602817;179602816
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: Ig-30
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.3907
• Predicted PPI site: I

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/I	None	None	0.606	N	0.293	0.251	0.40318662893	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1172	likely_benign	0.1239	benign	-0.826	Destabilizing	0.953	D	0.47	neutral	D	0.539205149	None	None	I
T/C	0.5793	likely_pathogenic	0.6145	pathogenic	-0.577	Destabilizing	1.0	D	0.565	neutral	None	None	None	None	I
T/D	0.5247	ambiguous	0.5578	ambiguous	-0.475	Destabilizing	0.998	D	0.517	neutral	None	None	None	None	I
T/E	0.3707	ambiguous	0.4196	ambiguous	-0.486	Destabilizing	0.985	D	0.508	neutral	None	None	None	None	I
T/F	0.2607	likely_benign	0.2721	benign	-0.966	Destabilizing	0.998	D	0.67	neutral	None	None	None	None	I
T/G	0.4354	ambiguous	0.4505	ambiguous	-1.068	Destabilizing	0.993	D	0.595	neutral	None	None	None	None	I
T/H	0.2457	likely_benign	0.2563	benign	-1.404	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	I
T/I	0.1858	likely_benign	0.2018	benign	-0.277	Destabilizing	0.606	D	0.293	neutral	N	0.512505032	None	None	I
T/K	0.2039	likely_benign	0.2214	benign	-0.785	Destabilizing	0.671	D	0.293	neutral	None	None	None	None	I
T/L	0.1167	likely_benign	0.125	benign	-0.277	Destabilizing	0.931	D	0.495	neutral	None	None	None	None	I
T/M	0.0965	likely_benign	0.1068	benign	0.076	Stabilizing	0.998	D	0.568	neutral	None	None	None	None	I
T/N	0.1505	likely_benign	0.1582	benign	-0.723	Destabilizing	0.997	D	0.461	neutral	N	0.513841015	None	None	I
T/P	0.7106	likely_pathogenic	0.711	pathogenic	-0.428	Destabilizing	0.999	D	0.559	neutral	D	0.721921747	None	None	I
T/Q	0.2378	likely_benign	0.2609	benign	-0.956	Destabilizing	0.996	D	0.571	neutral	None	None	None	None	I
T/R	0.1568	likely_benign	0.1748	benign	-0.514	Destabilizing	0.991	D	0.542	neutral	None	None	None	None	I
T/S	0.1403	likely_benign	0.1493	benign	-0.974	Destabilizing	0.98	D	0.484	neutral	N	0.512818854	None	None	I
T/V	0.1649	likely_benign	0.1802	benign	-0.428	Destabilizing	0.469	N	0.272	neutral	None	None	None	None	I
T/W	0.6116	likely_pathogenic	0.6629	pathogenic	-0.884	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
T/Y	0.306	likely_benign	0.3228	benign	-0.648	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	I

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.