TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18080	54463;54464;54465	chr2:178604851;178604850;178604849	chr2:179469578;179469577;179469576
N2AB	16439	49540;49541;49542	chr2:178604851;178604850;178604849	chr2:179469578;179469577;179469576
N2A	15512	46759;46760;46761	chr2:178604851;178604850;178604849	chr2:179469578;179469577;179469576
N2B	9015	27268;27269;27270	chr2:178604851;178604850;178604849	chr2:179469578;179469577;179469576
Novex-1	9140	27643;27644;27645	chr2:178604851;178604850;178604849	chr2:179469578;179469577;179469576
Novex-2	9207	27844;27845;27846	chr2:178604851;178604850;178604849	chr2:179469578;179469577;179469576
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: Fn3-19
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.4215
• 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	rs756321267	-0.129	0.581	N	0.55	0.27	0.251116650651	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
E/K	rs756321267	-0.129	0.581	N	0.55	0.27	0.251116650651	gnomAD-4.0.0	2.73903E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59999E-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	0.5311	ambiguous	0.4833	ambiguous	-0.985	Destabilizing	0.581	D	0.641	neutral	N	0.506667085	None	None	N
E/C	0.9763	likely_pathogenic	0.9735	pathogenic	-0.468	Destabilizing	0.993	D	0.724	prob.delet.	None	None	None	None	N
E/D	0.2085	likely_benign	0.2369	benign	-0.853	Destabilizing	0.004	N	0.197	neutral	N	0.432302612	None	None	N
E/F	0.9692	likely_pathogenic	0.9626	pathogenic	-0.449	Destabilizing	0.993	D	0.719	prob.delet.	None	None	None	None	N
E/G	0.469	ambiguous	0.4317	ambiguous	-1.313	Destabilizing	0.83	D	0.683	prob.neutral	N	0.496892808	None	None	N
E/H	0.8863	likely_pathogenic	0.8725	pathogenic	-0.582	Destabilizing	0.98	D	0.666	neutral	None	None	None	None	N
E/I	0.9185	likely_pathogenic	0.8853	pathogenic	-0.098	Destabilizing	0.929	D	0.741	deleterious	None	None	None	None	N
E/K	0.6806	likely_pathogenic	0.637	pathogenic	-0.46	Destabilizing	0.581	D	0.55	neutral	N	0.495103297	None	None	N
E/L	0.9088	likely_pathogenic	0.8811	pathogenic	-0.098	Destabilizing	0.929	D	0.735	prob.delet.	None	None	None	None	N
E/M	0.8911	likely_pathogenic	0.8612	pathogenic	0.295	Stabilizing	0.993	D	0.675	neutral	None	None	None	None	N
E/N	0.5295	ambiguous	0.517	ambiguous	-0.933	Destabilizing	0.764	D	0.697	prob.neutral	None	None	None	None	N
E/P	0.9858	likely_pathogenic	0.9837	pathogenic	-0.374	Destabilizing	0.929	D	0.717	prob.delet.	None	None	None	None	N
E/Q	0.4386	ambiguous	0.3991	ambiguous	-0.839	Destabilizing	0.83	D	0.663	neutral	N	0.500471831	None	None	N
E/R	0.7964	likely_pathogenic	0.76	pathogenic	-0.154	Destabilizing	0.866	D	0.695	prob.neutral	None	None	None	None	N
E/S	0.5054	ambiguous	0.4775	ambiguous	-1.221	Destabilizing	0.48	N	0.602	neutral	None	None	None	None	N
E/T	0.6177	likely_pathogenic	0.5634	ambiguous	-0.95	Destabilizing	0.866	D	0.706	prob.neutral	None	None	None	None	N
E/V	0.7855	likely_pathogenic	0.7309	pathogenic	-0.374	Destabilizing	0.908	D	0.733	prob.delet.	N	0.495562653	None	None	N
E/W	0.9889	likely_pathogenic	0.9875	pathogenic	-0.142	Destabilizing	0.993	D	0.733	prob.delet.	None	None	None	None	N
E/Y	0.9407	likely_pathogenic	0.9312	pathogenic	-0.185	Destabilizing	0.993	D	0.712	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.