TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33547	100864;100865;100866	chr2:178536108;178536107;178536106	chr2:179400835;179400834;179400833
N2AB	31906	95941;95942;95943	chr2:178536108;178536107;178536106	chr2:179400835;179400834;179400833
N2A	30979	93160;93161;93162	chr2:178536108;178536107;178536106	chr2:179400835;179400834;179400833
N2B	24482	73669;73670;73671	chr2:178536108;178536107;178536106	chr2:179400835;179400834;179400833
Novex-1	24607	74044;74045;74046	chr2:178536108;178536107;178536106	chr2:179400835;179400834;179400833
Novex-2	24674	74245;74246;74247	chr2:178536108;178536107;178536106	chr2:179400835;179400834;179400833
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-158
• Domain position: 52
• Structural Position: 126
• Q(SASA): 0.2902
• 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	rs1365402838	None	0.997	N	0.773	0.465	0.493156425868	gnomAD-4.0.0	5.4767E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.1995E-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
E/A	0.6228	likely_pathogenic	0.4769	ambiguous	-0.721	Destabilizing	0.995	D	0.746	deleterious	N	0.513278918	None	None	N
E/C	0.9901	likely_pathogenic	0.9786	pathogenic	-0.417	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
E/D	0.4844	ambiguous	0.3985	ambiguous	-0.654	Destabilizing	0.965	D	0.635	neutral	N	0.48297744	None	None	N
E/F	0.9917	likely_pathogenic	0.9812	pathogenic	-0.164	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
E/G	0.7771	likely_pathogenic	0.6352	pathogenic	-1.02	Destabilizing	1.0	D	0.726	prob.delet.	D	0.535310415	None	None	N
E/H	0.9579	likely_pathogenic	0.9068	pathogenic	-0.085	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
E/I	0.9175	likely_pathogenic	0.846	pathogenic	0.074	Stabilizing	0.999	D	0.756	deleterious	None	None	None	None	N
E/K	0.8638	likely_pathogenic	0.7196	pathogenic	-0.251	Destabilizing	0.997	D	0.773	deleterious	N	0.519378171	None	None	N
E/L	0.9611	likely_pathogenic	0.9189	pathogenic	0.074	Stabilizing	0.999	D	0.756	deleterious	None	None	None	None	N
E/M	0.942	likely_pathogenic	0.8934	pathogenic	0.252	Stabilizing	0.998	D	0.727	prob.delet.	None	None	None	None	N
E/N	0.7994	likely_pathogenic	0.6934	pathogenic	-0.731	Destabilizing	0.998	D	0.734	prob.delet.	None	None	None	None	N
E/P	0.9677	likely_pathogenic	0.9148	pathogenic	-0.171	Destabilizing	0.992	D	0.719	prob.delet.	None	None	None	None	N
E/Q	0.5795	likely_pathogenic	0.4286	ambiguous	-0.619	Destabilizing	0.999	D	0.705	prob.neutral	N	0.489095336	None	None	N
E/R	0.9266	likely_pathogenic	0.8379	pathogenic	0.133	Stabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
E/S	0.6924	likely_pathogenic	0.5599	ambiguous	-0.961	Destabilizing	0.997	D	0.743	deleterious	None	None	None	None	N
E/T	0.7145	likely_pathogenic	0.5736	pathogenic	-0.711	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
E/V	0.7793	likely_pathogenic	0.6557	pathogenic	-0.171	Destabilizing	0.998	D	0.762	deleterious	N	0.516529867	None	None	N
E/W	0.9981	likely_pathogenic	0.9948	pathogenic	0.126	Stabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
E/Y	0.9811	likely_pathogenic	0.9565	pathogenic	0.095	Stabilizing	1.0	D	0.738	prob.delet.	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.