TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19516	58771;58772;58773	chr2:178593754;178593753;178593752	chr2:179458481;179458480;179458479
N2AB	17875	53848;53849;53850	chr2:178593754;178593753;178593752	chr2:179458481;179458480;179458479
N2A	16948	51067;51068;51069	chr2:178593754;178593753;178593752	chr2:179458481;179458480;179458479
N2B	10451	31576;31577;31578	chr2:178593754;178593753;178593752	chr2:179458481;179458480;179458479
Novex-1	10576	31951;31952;31953	chr2:178593754;178593753;178593752	chr2:179458481;179458480;179458479
Novex-2	10643	32152;32153;32154	chr2:178593754;178593753;178593752	chr2:179458481;179458480;179458479
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-29
• Domain position: 38
• Structural Position: 39
• Q(SASA): 0.1725
• 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	rs776824040	-1.754	0.333	N	0.267	0.105	0.426084969639	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
I/V	rs776824040	-1.754	0.333	N	0.267	0.105	0.426084969639	gnomAD-4.0.0	1.59231E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85932E-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	0.7734	likely_pathogenic	0.7562	pathogenic	-2.462	Highly Destabilizing	0.992	D	0.563	neutral	None	None	None	None	I
I/C	0.7895	likely_pathogenic	0.7848	pathogenic	-1.853	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
I/D	0.9469	likely_pathogenic	0.9464	pathogenic	-2.811	Highly Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
I/E	0.8883	likely_pathogenic	0.8803	pathogenic	-2.7	Highly Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
I/F	0.3632	ambiguous	0.3936	ambiguous	-1.634	Destabilizing	0.998	D	0.66	neutral	N	0.518172157	None	None	I
I/G	0.9257	likely_pathogenic	0.9266	pathogenic	-2.902	Highly Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
I/H	0.7107	likely_pathogenic	0.7411	pathogenic	-2.197	Highly Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
I/K	0.6878	likely_pathogenic	0.6996	pathogenic	-1.91	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
I/L	0.2586	likely_benign	0.2536	benign	-1.239	Destabilizing	0.889	D	0.409	neutral	N	0.508416524	None	None	I
I/M	0.2392	likely_benign	0.2187	benign	-1.097	Destabilizing	0.998	D	0.677	prob.neutral	N	0.487827198	None	None	I
I/N	0.5574	ambiguous	0.5811	pathogenic	-2.023	Highly Destabilizing	0.999	D	0.745	deleterious	N	0.476898512	None	None	I
I/P	0.9941	likely_pathogenic	0.9929	pathogenic	-1.623	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
I/Q	0.7371	likely_pathogenic	0.7413	pathogenic	-2.093	Highly Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
I/R	0.5441	ambiguous	0.5735	pathogenic	-1.345	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
I/S	0.5936	likely_pathogenic	0.6055	pathogenic	-2.655	Highly Destabilizing	0.998	D	0.641	neutral	N	0.46509768	None	None	I
I/T	0.4707	ambiguous	0.4815	ambiguous	-2.421	Highly Destabilizing	0.989	D	0.609	neutral	N	0.480864563	None	None	I
I/V	0.114	likely_benign	0.0974	benign	-1.623	Destabilizing	0.333	N	0.267	neutral	N	0.45031237	None	None	I
I/W	0.8874	likely_pathogenic	0.9052	pathogenic	-1.917	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
I/Y	0.6898	likely_pathogenic	0.7461	pathogenic	-1.686	Destabilizing	1.0	D	0.689	prob.neutral	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.