TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14576	43951;43952;43953	chr2:178632168;178632167;178632166	chr2:179496895;179496894;179496893
N2AB	12935	39028;39029;39030	chr2:178632168;178632167;178632166	chr2:179496895;179496894;179496893
N2A	12008	36247;36248;36249	chr2:178632168;178632167;178632166	chr2:179496895;179496894;179496893
N2B	5511	16756;16757;16758	chr2:178632168;178632167;178632166	chr2:179496895;179496894;179496893
Novex-1	5636	17131;17132;17133	chr2:178632168;178632167;178632166	chr2:179496895;179496894;179496893
Novex-2	5703	17332;17333;17334	chr2:178632168;178632167;178632166	chr2:179496895;179496894;179496893
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-96
• Domain position: 80
• Structural Position: 171
• Q(SASA): 0.6219
• 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/D	rs2059887761	None	0.977	N	0.506	0.228	0.286081765059	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
E/D	rs2059887761	None	0.977	N	0.506	0.228	0.286081765059	gnomAD-4.0.0	1.31487E-05	None	None	None	None	N	None	4.82649E-05	0	None	0	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	0.2112	likely_benign	0.187	benign	-0.785	Destabilizing	0.955	D	0.643	neutral	N	0.488932438	None	None	N
E/C	0.9187	likely_pathogenic	0.9187	pathogenic	-0.229	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
E/D	0.2066	likely_benign	0.2071	benign	-0.747	Destabilizing	0.977	D	0.506	neutral	N	0.517863078	None	None	N
E/F	0.8074	likely_pathogenic	0.8044	pathogenic	-0.51	Destabilizing	0.998	D	0.724	prob.delet.	None	None	None	None	N
E/G	0.2611	likely_benign	0.2425	benign	-1.057	Destabilizing	0.993	D	0.71	prob.delet.	N	0.519239921	None	None	N
E/H	0.58	likely_pathogenic	0.5919	pathogenic	-0.578	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
E/I	0.456	ambiguous	0.428	ambiguous	-0.073	Destabilizing	0.995	D	0.725	prob.delet.	None	None	None	None	N
E/K	0.1533	likely_benign	0.1474	benign	-0.058	Destabilizing	0.977	D	0.601	neutral	N	0.484419235	None	None	N
E/L	0.5557	ambiguous	0.5345	ambiguous	-0.073	Destabilizing	0.99	D	0.698	prob.neutral	None	None	None	None	N
E/M	0.5314	ambiguous	0.5099	ambiguous	0.254	Stabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
E/N	0.3607	ambiguous	0.3522	ambiguous	-0.464	Destabilizing	0.995	D	0.709	prob.delet.	None	None	None	None	N
E/P	0.8887	likely_pathogenic	0.8948	pathogenic	-0.29	Destabilizing	0.998	D	0.771	deleterious	None	None	None	None	N
E/Q	0.1902	likely_benign	0.181	benign	-0.419	Destabilizing	0.997	D	0.683	prob.neutral	N	0.492091264	None	None	N
E/R	0.3081	likely_benign	0.3159	benign	0.143	Stabilizing	0.998	D	0.727	prob.delet.	None	None	None	None	N
E/S	0.2579	likely_benign	0.2374	benign	-0.679	Destabilizing	0.966	D	0.606	neutral	None	None	None	None	N
E/T	0.2419	likely_benign	0.2165	benign	-0.456	Destabilizing	0.43	N	0.407	neutral	None	None	None	None	N
E/V	0.2574	likely_benign	0.2353	benign	-0.29	Destabilizing	0.987	D	0.705	prob.neutral	N	0.487700293	None	None	N
E/W	0.9326	likely_pathogenic	0.9395	pathogenic	-0.266	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
E/Y	0.7333	likely_pathogenic	0.7383	pathogenic	-0.243	Destabilizing	0.999	D	0.746	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.