TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26504	79735;79736;79737	chr2:178566622;178566621;178566620	chr2:179431349;179431348;179431347
N2AB	24863	74812;74813;74814	chr2:178566622;178566621;178566620	chr2:179431349;179431348;179431347
N2A	23936	72031;72032;72033	chr2:178566622;178566621;178566620	chr2:179431349;179431348;179431347
N2B	17439	52540;52541;52542	chr2:178566622;178566621;178566620	chr2:179431349;179431348;179431347
Novex-1	17564	52915;52916;52917	chr2:178566622;178566621;178566620	chr2:179431349;179431348;179431347
Novex-2	17631	53116;53117;53118	chr2:178566622;178566621;178566620	chr2:179431349;179431348;179431347
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: Fn3-81
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.1099
• 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
I/V	rs200301756	-1.302	None	N	0.185	0.065	None	gnomAD-2.1.1	1.62E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	3.56E-05	0
I/V	rs200301756	-1.302	None	N	0.185	0.065	None	gnomAD-4.0.0	1.09557E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.07945E-05	0	6.62822E-05

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	0.6438	likely_pathogenic	0.6329	pathogenic	-2.996	Highly Destabilizing	0.072	N	0.657	neutral	None	None	None	None	N
I/C	0.8002	likely_pathogenic	0.7891	pathogenic	-2.952	Highly Destabilizing	0.909	D	0.774	deleterious	None	None	None	None	N
I/D	0.9962	likely_pathogenic	0.9965	pathogenic	-3.497	Highly Destabilizing	0.726	D	0.821	deleterious	None	None	None	None	N
I/E	0.9905	likely_pathogenic	0.991	pathogenic	-3.209	Highly Destabilizing	0.726	D	0.802	deleterious	None	None	None	None	N
I/F	0.4284	ambiguous	0.4288	ambiguous	-1.887	Destabilizing	0.497	N	0.703	prob.neutral	N	0.483434835	None	None	N
I/G	0.9576	likely_pathogenic	0.9585	pathogenic	-3.582	Highly Destabilizing	0.726	D	0.772	deleterious	None	None	None	None	N
I/H	0.9803	likely_pathogenic	0.9822	pathogenic	-3.074	Highly Destabilizing	0.968	D	0.813	deleterious	None	None	None	None	N
I/K	0.9765	likely_pathogenic	0.9797	pathogenic	-2.343	Highly Destabilizing	0.726	D	0.802	deleterious	None	None	None	None	N
I/L	0.1644	likely_benign	0.1516	benign	-1.253	Destabilizing	0.025	N	0.398	neutral	N	0.508656092	None	None	N
I/M	0.1717	likely_benign	0.1635	benign	-1.718	Destabilizing	0.497	N	0.673	neutral	N	0.474547292	None	None	N
I/N	0.9522	likely_pathogenic	0.9576	pathogenic	-2.939	Highly Destabilizing	0.859	D	0.819	deleterious	N	0.505021811	None	None	N
I/P	0.9918	likely_pathogenic	0.9925	pathogenic	-1.822	Destabilizing	0.89	D	0.822	deleterious	None	None	None	None	N
I/Q	0.9744	likely_pathogenic	0.9769	pathogenic	-2.687	Highly Destabilizing	0.89	D	0.826	deleterious	None	None	None	None	N
I/R	0.9582	likely_pathogenic	0.9644	pathogenic	-2.197	Highly Destabilizing	0.726	D	0.822	deleterious	None	None	None	None	N
I/S	0.8688	likely_pathogenic	0.8806	pathogenic	-3.639	Highly Destabilizing	0.497	N	0.769	deleterious	N	0.516124626	None	None	N
I/T	0.7968	likely_pathogenic	0.8113	pathogenic	-3.184	Highly Destabilizing	0.124	N	0.728	prob.delet.	N	0.515871137	None	None	N
I/V	0.0671	likely_benign	0.0663	benign	-1.822	Destabilizing	None	N	0.185	neutral	N	0.421687682	None	None	N
I/W	0.9789	likely_pathogenic	0.9805	pathogenic	-2.184	Highly Destabilizing	0.968	D	0.805	deleterious	None	None	None	None	N
I/Y	0.9083	likely_pathogenic	0.9166	pathogenic	-2.008	Highly Destabilizing	0.726	D	0.803	deleterious	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.