TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22087	66484;66485;66486	chr2:178582110;178582109;178582108	chr2:179446837;179446836;179446835
N2AB	20446	61561;61562;61563	chr2:178582110;178582109;178582108	chr2:179446837;179446836;179446835
N2A	19519	58780;58781;58782	chr2:178582110;178582109;178582108	chr2:179446837;179446836;179446835
N2B	13022	39289;39290;39291	chr2:178582110;178582109;178582108	chr2:179446837;179446836;179446835
Novex-1	13147	39664;39665;39666	chr2:178582110;178582109;178582108	chr2:179446837;179446836;179446835
Novex-2	13214	39865;39866;39867	chr2:178582110;178582109;178582108	chr2:179446837;179446836;179446835
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: Fn3-48
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.2037
• 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/V	None	None	0.993	D	0.377	0.267	0.59450981025	gnomAD-4.0.0	1.59318E-06	None	None	None	None	I	None	5.6638E-05	0	None	0	0	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
I/A	0.9809	likely_pathogenic	0.9621	pathogenic	-2.383	Highly Destabilizing	0.999	D	0.675	neutral	None	None	None	None	I
I/C	0.9914	likely_pathogenic	0.9807	pathogenic	-1.536	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
I/D	0.9995	likely_pathogenic	0.9988	pathogenic	-2.595	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	I
I/E	0.9975	likely_pathogenic	0.9949	pathogenic	-2.468	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	I
I/F	0.975	likely_pathogenic	0.9385	pathogenic	-1.578	Destabilizing	1.0	D	0.835	deleterious	D	0.551693205	None	None	I
I/G	0.9987	likely_pathogenic	0.9968	pathogenic	-2.837	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	I
I/H	0.9992	likely_pathogenic	0.9974	pathogenic	-2.238	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	I
I/K	0.9964	likely_pathogenic	0.9924	pathogenic	-1.81	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	I
I/L	0.6048	likely_pathogenic	0.4231	ambiguous	-1.115	Destabilizing	0.993	D	0.401	neutral	N	0.494075531	None	None	I
I/M	0.7941	likely_pathogenic	0.6476	pathogenic	-0.851	Destabilizing	1.0	D	0.816	deleterious	D	0.5542281	None	None	I
I/N	0.9916	likely_pathogenic	0.9828	pathogenic	-1.908	Destabilizing	1.0	D	0.887	deleterious	D	0.543721169	None	None	I
I/P	0.9808	likely_pathogenic	0.9725	pathogenic	-1.514	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	I
I/Q	0.9975	likely_pathogenic	0.994	pathogenic	-1.94	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	I
I/R	0.9954	likely_pathogenic	0.9902	pathogenic	-1.3	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	I
I/S	0.9921	likely_pathogenic	0.9826	pathogenic	-2.542	Highly Destabilizing	1.0	D	0.874	deleterious	D	0.5429607	None	None	I
I/T	0.9787	likely_pathogenic	0.9629	pathogenic	-2.292	Highly Destabilizing	1.0	D	0.851	deleterious	N	0.51827308	None	None	I
I/V	0.0942	likely_benign	0.0817	benign	-1.514	Destabilizing	0.993	D	0.377	neutral	D	0.523332835	None	None	I
I/W	0.9997	likely_pathogenic	0.999	pathogenic	-1.915	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	I
I/Y	0.9974	likely_pathogenic	0.9934	pathogenic	-1.652	Destabilizing	1.0	D	0.883	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.