TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26207	78844;78845;78846	chr2:178567513;178567512;178567511	chr2:179432240;179432239;179432238
N2AB	24566	73921;73922;73923	chr2:178567513;178567512;178567511	chr2:179432240;179432239;179432238
N2A	23639	71140;71141;71142	chr2:178567513;178567512;178567511	chr2:179432240;179432239;179432238
N2B	17142	51649;51650;51651	chr2:178567513;178567512;178567511	chr2:179432240;179432239;179432238
Novex-1	17267	52024;52025;52026	chr2:178567513;178567512;178567511	chr2:179432240;179432239;179432238
Novex-2	17334	52225;52226;52227	chr2:178567513;178567512;178567511	chr2:179432240;179432239;179432238
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-137
• Domain position: 15
• Structural Position: 23
• Q(SASA): 0.5369
• 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
A/T	None	None	1.0	N	0.725	0.348	0.236278675362	gnomAD-4.0.0	1.59445E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.88558E-05	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
A/C	0.8076	likely_pathogenic	0.8253	pathogenic	-0.734	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
A/D	0.9684	likely_pathogenic	0.9791	pathogenic	-1.118	Destabilizing	1.0	D	0.806	deleterious	N	0.482647914	None	None	I
A/E	0.9148	likely_pathogenic	0.9435	pathogenic	-1.271	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
A/F	0.9248	likely_pathogenic	0.9365	pathogenic	-1.218	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
A/G	0.5152	ambiguous	0.5291	ambiguous	-0.697	Destabilizing	1.0	D	0.541	neutral	N	0.509399449	None	None	I
A/H	0.9345	likely_pathogenic	0.9484	pathogenic	-0.798	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
A/I	0.809	likely_pathogenic	0.8535	pathogenic	-0.558	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
A/K	0.9301	likely_pathogenic	0.9524	pathogenic	-0.968	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	I
A/L	0.8034	likely_pathogenic	0.838	pathogenic	-0.558	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
A/M	0.7811	likely_pathogenic	0.8155	pathogenic	-0.315	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
A/N	0.8922	likely_pathogenic	0.9158	pathogenic	-0.568	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
A/P	0.9656	likely_pathogenic	0.9712	pathogenic	-0.539	Destabilizing	1.0	D	0.769	deleterious	N	0.467808888	None	None	I
A/Q	0.8405	likely_pathogenic	0.8789	pathogenic	-0.922	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	I
A/R	0.8375	likely_pathogenic	0.8751	pathogenic	-0.404	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
A/S	0.2372	likely_benign	0.2393	benign	-0.729	Destabilizing	1.0	D	0.55	neutral	N	0.473164486	None	None	I
A/T	0.4895	ambiguous	0.5481	ambiguous	-0.818	Destabilizing	1.0	D	0.725	prob.delet.	N	0.473898501	None	None	I
A/V	0.5145	ambiguous	0.5743	pathogenic	-0.539	Destabilizing	1.0	D	0.645	neutral	N	0.452094035	None	None	I
A/W	0.9902	likely_pathogenic	0.9913	pathogenic	-1.365	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
A/Y	0.9555	likely_pathogenic	0.9637	pathogenic	-1.033	Destabilizing	1.0	D	0.807	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.