TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21454	64585;64586;64587	chr2:178586541;178586540;178586539	chr2:179451268;179451267;179451266
N2AB	19813	59662;59663;59664	chr2:178586541;178586540;178586539	chr2:179451268;179451267;179451266
N2A	18886	56881;56882;56883	chr2:178586541;178586540;178586539	chr2:179451268;179451267;179451266
N2B	12389	37390;37391;37392	chr2:178586541;178586540;178586539	chr2:179451268;179451267;179451266
Novex-1	12514	37765;37766;37767	chr2:178586541;178586540;178586539	chr2:179451268;179451267;179451266
Novex-2	12581	37966;37967;37968	chr2:178586541;178586540;178586539	chr2:179451268;179451267;179451266
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: Fn3-43
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.3138
• 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/A	rs373183196	-0.67	0.997	N	0.787	0.335	None	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

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	0.588	likely_pathogenic	0.528	ambiguous	-0.701	Destabilizing	0.997	D	0.787	deleterious	N	0.518825518	None	None	N
E/C	0.9763	likely_pathogenic	0.9704	pathogenic	-0.516	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
E/D	0.3658	ambiguous	0.3559	ambiguous	-1.122	Destabilizing	0.997	D	0.733	deleterious	N	0.501989197	None	None	N
E/F	0.9367	likely_pathogenic	0.9216	pathogenic	0.123	Stabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
E/G	0.7486	likely_pathogenic	0.6955	pathogenic	-1.098	Destabilizing	0.999	D	0.707	prob.delet.	N	0.518998877	None	None	N
E/H	0.9109	likely_pathogenic	0.8874	pathogenic	-0.095	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
E/I	0.6748	likely_pathogenic	0.6161	pathogenic	0.39	Stabilizing	0.999	D	0.821	deleterious	None	None	None	None	N
E/K	0.7431	likely_pathogenic	0.6679	pathogenic	-0.707	Destabilizing	0.997	D	0.813	deleterious	N	0.519806953	None	None	N
E/L	0.7496	likely_pathogenic	0.701	pathogenic	0.39	Stabilizing	0.999	D	0.728	deleterious	None	None	None	None	N
E/M	0.7752	likely_pathogenic	0.7246	pathogenic	0.721	Stabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
E/N	0.8019	likely_pathogenic	0.7622	pathogenic	-1.261	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
E/P	0.9052	likely_pathogenic	0.8878	pathogenic	0.048	Stabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
E/Q	0.5305	ambiguous	0.4685	ambiguous	-1.083	Destabilizing	0.999	D	0.79	deleterious	N	0.513438341	None	None	N
E/R	0.851	likely_pathogenic	0.8111	pathogenic	-0.321	Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
E/S	0.7395	likely_pathogenic	0.6934	pathogenic	-1.582	Destabilizing	0.998	D	0.812	deleterious	None	None	None	None	N
E/T	0.6599	likely_pathogenic	0.607	pathogenic	-1.25	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
E/V	0.4703	ambiguous	0.4174	ambiguous	0.048	Stabilizing	0.999	D	0.755	deleterious	N	0.515459926	None	None	N
E/W	0.9833	likely_pathogenic	0.9788	pathogenic	0.395	Stabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
E/Y	0.9198	likely_pathogenic	0.8937	pathogenic	0.375	Stabilizing	1.0	D	0.853	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.