TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34341	103246;103247;103248	chr2:178533594;178533593;178533592	chr2:179398321;179398320;179398319
N2AB	32700	98323;98324;98325	chr2:178533594;178533593;178533592	chr2:179398321;179398320;179398319
N2A	31773	95542;95543;95544	chr2:178533594;178533593;178533592	chr2:179398321;179398320;179398319
N2B	25276	76051;76052;76053	chr2:178533594;178533593;178533592	chr2:179398321;179398320;179398319
Novex-1	25401	76426;76427;76428	chr2:178533594;178533593;178533592	chr2:179398321;179398320;179398319
Novex-2	25468	76627;76628;76629	chr2:178533594;178533593;178533592	chr2:179398321;179398320;179398319
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-161
• Domain position: 84
• Structural Position: 165
• Q(SASA): 0.6195
• 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
E/D	rs1330415230	-0.33	0.046	N	0.261	0.111	0.326881540566	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	5.57E-05	None	0	None	0	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
E/A	0.4469	ambiguous	0.3955	ambiguous	-0.47	Destabilizing	0.885	D	0.634	neutral	N	0.491710399	None	None	I
E/C	0.9698	likely_pathogenic	0.9675	pathogenic	-0.072	Destabilizing	0.999	D	0.728	prob.delet.	None	None	None	None	I
E/D	0.4419	ambiguous	0.3909	ambiguous	-0.47	Destabilizing	0.046	N	0.261	neutral	N	0.488520848	None	None	I
E/F	0.9521	likely_pathogenic	0.936	pathogenic	-0.31	Destabilizing	0.998	D	0.706	prob.neutral	None	None	None	None	I
E/G	0.6218	likely_pathogenic	0.5579	ambiguous	-0.691	Destabilizing	0.046	N	0.447	neutral	N	0.509031413	None	None	I
E/H	0.8681	likely_pathogenic	0.8492	pathogenic	-0.2	Destabilizing	0.999	D	0.606	neutral	None	None	None	None	I
E/I	0.7419	likely_pathogenic	0.6926	pathogenic	0.086	Stabilizing	0.998	D	0.71	prob.delet.	None	None	None	None	I
E/K	0.4126	ambiguous	0.369	ambiguous	0.232	Stabilizing	0.939	D	0.629	neutral	N	0.508891818	None	None	I
E/L	0.8413	likely_pathogenic	0.8071	pathogenic	0.086	Stabilizing	0.993	D	0.697	prob.neutral	None	None	None	None	I
E/M	0.7445	likely_pathogenic	0.7121	pathogenic	0.239	Stabilizing	0.999	D	0.704	prob.neutral	None	None	None	None	I
E/N	0.6987	likely_pathogenic	0.637	pathogenic	-0.092	Destabilizing	0.986	D	0.598	neutral	None	None	None	None	I
E/P	0.9946	likely_pathogenic	0.9937	pathogenic	-0.079	Destabilizing	0.998	D	0.649	neutral	None	None	None	None	I
E/Q	0.3146	likely_benign	0.2985	benign	-0.066	Destabilizing	0.991	D	0.577	neutral	D	0.531443391	None	None	I
E/R	0.6344	likely_pathogenic	0.5973	pathogenic	0.427	Stabilizing	0.993	D	0.63	neutral	None	None	None	None	I
E/S	0.4707	ambiguous	0.4214	ambiguous	-0.272	Destabilizing	0.953	D	0.611	neutral	None	None	None	None	I
E/T	0.5135	ambiguous	0.4647	ambiguous	-0.093	Destabilizing	0.993	D	0.592	neutral	None	None	None	None	I
E/V	0.5244	ambiguous	0.4744	ambiguous	-0.079	Destabilizing	0.991	D	0.672	neutral	N	0.492079247	None	None	I
E/W	0.9838	likely_pathogenic	0.9806	pathogenic	-0.133	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	I
E/Y	0.9226	likely_pathogenic	0.9065	pathogenic	-0.056	Destabilizing	0.998	D	0.692	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.