TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28309	85150;85151;85152	chr2:178561207;178561206;178561205	chr2:179425934;179425933;179425932
N2AB	26668	80227;80228;80229	chr2:178561207;178561206;178561205	chr2:179425934;179425933;179425932
N2A	25741	77446;77447;77448	chr2:178561207;178561206;178561205	chr2:179425934;179425933;179425932
N2B	19244	57955;57956;57957	chr2:178561207;178561206;178561205	chr2:179425934;179425933;179425932
Novex-1	19369	58330;58331;58332	chr2:178561207;178561206;178561205	chr2:179425934;179425933;179425932
Novex-2	19436	58531;58532;58533	chr2:178561207;178561206;178561205	chr2:179425934;179425933;179425932
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: Fn3-94
• Domain position: 58
• Structural Position: 88
• Q(SASA): 0.1978
• 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
E/K	rs1383001734	0.134	0.994	N	0.431	0.371	0.340510301474	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	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	0.2536	likely_benign	0.2412	benign	-0.212	Destabilizing	0.994	D	0.511	neutral	N	0.511651617	None	None	N
E/C	0.9155	likely_pathogenic	0.9142	pathogenic	-0.368	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
E/D	0.0781	likely_benign	0.0718	benign	-0.602	Destabilizing	0.104	N	0.131	neutral	N	0.433289621	None	None	N
E/F	0.9047	likely_pathogenic	0.903	pathogenic	0.374	Stabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
E/G	0.1887	likely_benign	0.1708	benign	-0.493	Destabilizing	0.994	D	0.535	neutral	N	0.51282784	None	None	N
E/H	0.6519	likely_pathogenic	0.6111	pathogenic	0.746	Stabilizing	1.0	D	0.622	neutral	None	None	None	None	N
E/I	0.6791	likely_pathogenic	0.6918	pathogenic	0.524	Stabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
E/K	0.321	likely_benign	0.2891	benign	0.226	Stabilizing	0.994	D	0.431	neutral	N	0.503013491	None	None	N
E/L	0.6727	likely_pathogenic	0.6686	pathogenic	0.524	Stabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
E/M	0.6769	likely_pathogenic	0.6673	pathogenic	0.348	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
E/N	0.2305	likely_benign	0.2	benign	-0.483	Destabilizing	0.998	D	0.573	neutral	None	None	None	None	N
E/P	0.8927	likely_pathogenic	0.8886	pathogenic	0.3	Stabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
E/Q	0.2463	likely_benign	0.2275	benign	-0.352	Destabilizing	0.998	D	0.564	neutral	N	0.486121241	None	None	N
E/R	0.5297	ambiguous	0.494	ambiguous	0.656	Stabilizing	0.999	D	0.631	neutral	None	None	None	None	N
E/S	0.2708	likely_benign	0.2445	benign	-0.633	Destabilizing	0.992	D	0.448	neutral	None	None	None	None	N
E/T	0.3345	likely_benign	0.3141	benign	-0.378	Destabilizing	0.999	D	0.621	neutral	None	None	None	None	N
E/V	0.4248	ambiguous	0.4404	ambiguous	0.3	Stabilizing	0.999	D	0.673	neutral	N	0.517252225	None	None	N
E/W	0.9641	likely_pathogenic	0.9596	pathogenic	0.61	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/Y	0.7718	likely_pathogenic	0.7533	pathogenic	0.654	Stabilizing	1.0	D	0.685	prob.neutral	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.