TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33600	101023;101024;101025	chr2:178535817;178535816;178535815	chr2:179400544;179400543;179400542
N2AB	31959	96100;96101;96102	chr2:178535817;178535816;178535815	chr2:179400544;179400543;179400542
N2A	31032	93319;93320;93321	chr2:178535817;178535816;178535815	chr2:179400544;179400543;179400542
N2B	24535	73828;73829;73830	chr2:178535817;178535816;178535815	chr2:179400544;179400543;179400542
Novex-1	24660	74203;74204;74205	chr2:178535817;178535816;178535815	chr2:179400544;179400543;179400542
Novex-2	24727	74404;74405;74406	chr2:178535817;178535816;178535815	chr2:179400544;179400543;179400542
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-159
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.7587
• 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/K	None	None	0.916	N	0.555	0.189	0.18995819373	gnomAD-4.0.0	6.92294E-07	None	None	None	None	I	None	0	0	None	3.90046E-05	0	None	0	0	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	0.226	likely_benign	0.221	benign	-0.231	Destabilizing	0.921	D	0.553	neutral	N	0.468252264	None	None	I
E/C	0.9472	likely_pathogenic	0.9293	pathogenic	-0.045	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	I
E/D	0.2459	likely_benign	0.2196	benign	-0.178	Destabilizing	0.384	N	0.541	neutral	N	0.44991722	None	None	I
E/F	0.9376	likely_pathogenic	0.9167	pathogenic	-0.115	Destabilizing	0.998	D	0.751	deleterious	None	None	None	None	I
E/G	0.3619	ambiguous	0.3065	benign	-0.403	Destabilizing	0.987	D	0.641	neutral	N	0.449743861	None	None	I
E/H	0.731	likely_pathogenic	0.689	pathogenic	0.233	Stabilizing	0.993	D	0.613	neutral	None	None	None	None	I
E/I	0.628	likely_pathogenic	0.6158	pathogenic	0.181	Stabilizing	0.997	D	0.758	deleterious	None	None	None	None	I
E/K	0.3775	ambiguous	0.3508	ambiguous	0.447	Stabilizing	0.916	D	0.555	neutral	N	0.404739504	None	None	I
E/L	0.6212	likely_pathogenic	0.596	pathogenic	0.181	Stabilizing	0.979	D	0.705	prob.neutral	None	None	None	None	I
E/M	0.7019	likely_pathogenic	0.6857	pathogenic	0.162	Stabilizing	0.995	D	0.726	prob.delet.	None	None	None	None	I
E/N	0.493	ambiguous	0.4625	ambiguous	0.112	Stabilizing	0.978	D	0.587	neutral	None	None	None	None	I
E/P	0.8677	likely_pathogenic	0.8207	pathogenic	0.064	Stabilizing	0.977	D	0.683	prob.neutral	None	None	None	None	I
E/Q	0.2172	likely_benign	0.2161	benign	0.163	Stabilizing	0.376	N	0.255	neutral	N	0.396274736	None	None	I
E/R	0.5366	ambiguous	0.4858	ambiguous	0.639	Stabilizing	0.966	D	0.569	neutral	None	None	None	None	I
E/S	0.3306	likely_benign	0.3007	benign	-0.036	Destabilizing	0.939	D	0.53	neutral	None	None	None	None	I
E/T	0.368	ambiguous	0.3475	ambiguous	0.115	Stabilizing	0.977	D	0.621	neutral	None	None	None	None	I
E/V	0.3822	ambiguous	0.3776	ambiguous	0.064	Stabilizing	0.981	D	0.677	prob.neutral	N	0.448530353	None	None	I
E/W	0.9786	likely_pathogenic	0.9692	pathogenic	0.012	Stabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
E/Y	0.8769	likely_pathogenic	0.8364	pathogenic	0.124	Stabilizing	0.999	D	0.733	prob.delet.	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.