TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26525	79798;79799;79800	chr2:178566559;178566558;178566557	chr2:179431286;179431285;179431284
N2AB	24884	74875;74876;74877	chr2:178566559;178566558;178566557	chr2:179431286;179431285;179431284
N2A	23957	72094;72095;72096	chr2:178566559;178566558;178566557	chr2:179431286;179431285;179431284
N2B	17460	52603;52604;52605	chr2:178566559;178566558;178566557	chr2:179431286;179431285;179431284
Novex-1	17585	52978;52979;52980	chr2:178566559;178566558;178566557	chr2:179431286;179431285;179431284
Novex-2	17652	53179;53180;53181	chr2:178566559;178566558;178566557	chr2:179431286;179431285;179431284
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: Fn3-81
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1436
• 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/G	rs760756282	-2.421	1.0	D	0.782	0.589	0.477298106951	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
E/G	rs760756282	-2.421	1.0	D	0.782	0.589	0.477298106951	gnomAD-4.0.0	2.73782E-06	None	None	None	None	N	None	0	2.23624E-05	None	0	0	None	0	0	2.69853E-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	0.5462	ambiguous	0.6481	pathogenic	-1.5	Destabilizing	0.999	D	0.687	prob.neutral	D	0.537989361	None	None	N
E/C	0.9633	likely_pathogenic	0.9747	pathogenic	-0.707	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
E/D	0.6899	likely_pathogenic	0.7375	pathogenic	-1.797	Destabilizing	0.999	D	0.625	neutral	N	0.50878229	None	None	N
E/F	0.9694	likely_pathogenic	0.9815	pathogenic	-1.196	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
E/G	0.6777	likely_pathogenic	0.7579	pathogenic	-1.878	Destabilizing	1.0	D	0.782	deleterious	D	0.539763788	None	None	N
E/H	0.8785	likely_pathogenic	0.9203	pathogenic	-1.068	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/I	0.9267	likely_pathogenic	0.943	pathogenic	-0.41	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
E/K	0.7418	likely_pathogenic	0.7968	pathogenic	-1.559	Destabilizing	0.999	D	0.685	prob.neutral	N	0.511869709	None	None	N
E/L	0.899	likely_pathogenic	0.9293	pathogenic	-0.41	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/M	0.8536	likely_pathogenic	0.8934	pathogenic	0.306	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/N	0.854	likely_pathogenic	0.8795	pathogenic	-1.784	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/P	0.9985	likely_pathogenic	0.9988	pathogenic	-0.76	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
E/Q	0.2977	likely_benign	0.3658	ambiguous	-1.478	Destabilizing	1.0	D	0.744	deleterious	N	0.469722943	None	None	N
E/R	0.8389	likely_pathogenic	0.8833	pathogenic	-1.394	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
E/S	0.617	likely_pathogenic	0.6838	pathogenic	-2.379	Highly Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
E/T	0.8294	likely_pathogenic	0.8627	pathogenic	-2.019	Highly Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
E/V	0.8286	likely_pathogenic	0.8616	pathogenic	-0.76	Destabilizing	1.0	D	0.787	deleterious	N	0.520645575	None	None	N
E/W	0.9898	likely_pathogenic	0.9942	pathogenic	-1.327	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
E/Y	0.9408	likely_pathogenic	0.9631	pathogenic	-1.038	Destabilizing	1.0	D	0.807	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.