TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20896	62911;62912;62913	chr2:178589039;178589038;178589037	chr2:179453766;179453765;179453764
N2AB	19255	57988;57989;57990	chr2:178589039;178589038;178589037	chr2:179453766;179453765;179453764
N2A	18328	55207;55208;55209	chr2:178589039;178589038;178589037	chr2:179453766;179453765;179453764
N2B	11831	35716;35717;35718	chr2:178589039;178589038;178589037	chr2:179453766;179453765;179453764
Novex-1	11956	36091;36092;36093	chr2:178589039;178589038;178589037	chr2:179453766;179453765;179453764
Novex-2	12023	36292;36293;36294	chr2:178589039;178589038;178589037	chr2:179453766;179453765;179453764
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-39
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1666
• Predicted PPI site: I

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
I/M	None	None	0.994	D	0.659	0.417	0.614155820699	gnomAD-4.0.0	1.60181E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86022E-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
I/A	0.9888	likely_pathogenic	0.9889	pathogenic	-2.488	Highly Destabilizing	0.931	D	0.687	prob.neutral	None	None	None	None	I
I/C	0.9866	likely_pathogenic	0.9882	pathogenic	-1.438	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I
I/D	0.9989	likely_pathogenic	0.9987	pathogenic	-2.667	Highly Destabilizing	0.999	D	0.838	deleterious	None	None	None	None	I
I/E	0.9963	likely_pathogenic	0.996	pathogenic	-2.586	Highly Destabilizing	0.999	D	0.834	deleterious	None	None	None	None	I
I/F	0.9272	likely_pathogenic	0.9272	pathogenic	-1.724	Destabilizing	0.994	D	0.687	prob.neutral	D	0.525688912	None	None	I
I/G	0.9973	likely_pathogenic	0.997	pathogenic	-2.903	Highly Destabilizing	0.999	D	0.846	deleterious	None	None	None	None	I
I/H	0.9974	likely_pathogenic	0.9973	pathogenic	-2.258	Highly Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	I
I/K	0.9899	likely_pathogenic	0.9907	pathogenic	-1.881	Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	I
I/L	0.4623	ambiguous	0.4626	ambiguous	-1.336	Destabilizing	0.689	D	0.391	neutral	N	0.480085879	None	None	I
I/M	0.6186	likely_pathogenic	0.6302	pathogenic	-0.892	Destabilizing	0.994	D	0.659	neutral	D	0.528223807	None	None	I
I/N	0.9745	likely_pathogenic	0.9731	pathogenic	-1.814	Destabilizing	0.998	D	0.841	deleterious	D	0.529237765	None	None	I
I/P	0.9736	likely_pathogenic	0.9721	pathogenic	-1.697	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	I
I/Q	0.9941	likely_pathogenic	0.9939	pathogenic	-1.922	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	I
I/R	0.9901	likely_pathogenic	0.9903	pathogenic	-1.275	Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	I
I/S	0.9891	likely_pathogenic	0.9883	pathogenic	-2.389	Highly Destabilizing	0.994	D	0.827	deleterious	D	0.528477296	None	None	I
I/T	0.9729	likely_pathogenic	0.9737	pathogenic	-2.196	Highly Destabilizing	0.961	D	0.739	prob.delet.	N	0.521893931	None	None	I
I/V	0.2122	likely_benign	0.2201	benign	-1.697	Destabilizing	0.122	N	0.211	neutral	N	0.473770806	None	None	I
I/W	0.9976	likely_pathogenic	0.9974	pathogenic	-2.0	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
I/Y	0.9873	likely_pathogenic	0.9877	pathogenic	-1.811	Destabilizing	0.999	D	0.768	deleterious	None	None	None	None	I

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.