TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28195	84808;84809;84810	chr2:178561549;178561548;178561547	chr2:179426276;179426275;179426274
N2AB	26554	79885;79886;79887	chr2:178561549;178561548;178561547	chr2:179426276;179426275;179426274
N2A	25627	77104;77105;77106	chr2:178561549;178561548;178561547	chr2:179426276;179426275;179426274
N2B	19130	57613;57614;57615	chr2:178561549;178561548;178561547	chr2:179426276;179426275;179426274
Novex-1	19255	57988;57989;57990	chr2:178561549;178561548;178561547	chr2:179426276;179426275;179426274
Novex-2	19322	58189;58190;58191	chr2:178561549;178561548;178561547	chr2:179426276;179426275;179426274
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: Fn3-93
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.4791
• 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	None	None	0.978	N	0.56	0.45	0.504480301252	gnomAD-4.0.0	1.59262E-06	None	None	None	None	N	None	0	0	None	0	2.77948E-05	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	0.6117	likely_pathogenic	0.5999	pathogenic	-1.071	Destabilizing	0.989	D	0.585	neutral	N	0.499730163	None	None	N
E/C	0.9827	likely_pathogenic	0.9826	pathogenic	-0.516	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/D	0.3572	ambiguous	0.3103	benign	-1.152	Destabilizing	0.054	N	0.141	neutral	N	0.464687176	None	None	N
E/F	0.9904	likely_pathogenic	0.9896	pathogenic	-0.398	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/G	0.6227	likely_pathogenic	0.6083	pathogenic	-1.449	Destabilizing	0.978	D	0.56	neutral	N	0.493008666	None	None	N
E/H	0.9456	likely_pathogenic	0.945	pathogenic	-0.565	Destabilizing	1.0	D	0.609	neutral	None	None	None	None	N
E/I	0.9408	likely_pathogenic	0.9351	pathogenic	-0.029	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
E/K	0.7705	likely_pathogenic	0.7926	pathogenic	-0.575	Destabilizing	0.978	D	0.493	neutral	N	0.511054184	None	None	N
E/L	0.8979	likely_pathogenic	0.8993	pathogenic	-0.029	Destabilizing	0.998	D	0.762	deleterious	None	None	None	None	N
E/M	0.9225	likely_pathogenic	0.9154	pathogenic	0.511	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
E/N	0.7977	likely_pathogenic	0.7654	pathogenic	-1.22	Destabilizing	0.995	D	0.586	neutral	None	None	None	None	N
E/P	0.8411	likely_pathogenic	0.8424	pathogenic	-0.356	Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	N
E/Q	0.5179	ambiguous	0.5169	ambiguous	-1.066	Destabilizing	0.997	D	0.573	neutral	N	0.486599431	None	None	N
E/R	0.8664	likely_pathogenic	0.8768	pathogenic	-0.261	Destabilizing	0.998	D	0.651	neutral	None	None	None	None	N
E/S	0.7448	likely_pathogenic	0.722	pathogenic	-1.523	Destabilizing	0.983	D	0.509	neutral	None	None	None	None	N
E/T	0.8809	likely_pathogenic	0.8669	pathogenic	-1.192	Destabilizing	0.998	D	0.642	neutral	None	None	None	None	N
E/V	0.8286	likely_pathogenic	0.8215	pathogenic	-0.356	Destabilizing	0.999	D	0.724	prob.delet.	N	0.493008666	None	None	N
E/W	0.9957	likely_pathogenic	0.9955	pathogenic	-0.053	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
E/Y	0.9759	likely_pathogenic	0.9731	pathogenic	-0.112	Destabilizing	1.0	D	0.731	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.