TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19688	59287;59288;59289	chr2:178593057;178593056;178593055	chr2:179457784;179457783;179457782
N2AB	18047	54364;54365;54366	chr2:178593057;178593056;178593055	chr2:179457784;179457783;179457782
N2A	17120	51583;51584;51585	chr2:178593057;178593056;178593055	chr2:179457784;179457783;179457782
N2B	10623	32092;32093;32094	chr2:178593057;178593056;178593055	chr2:179457784;179457783;179457782
Novex-1	10748	32467;32468;32469	chr2:178593057;178593056;178593055	chr2:179457784;179457783;179457782
Novex-2	10815	32668;32669;32670	chr2:178593057;178593056;178593055	chr2:179457784;179457783;179457782
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-31
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5136
• 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
E/Q	None	None	0.31	N	0.269	0.185	0.282179105231	gnomAD-4.0.0	1.59269E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86002E-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
E/A	0.1736	likely_benign	0.1582	benign	-0.666	Destabilizing	0.826	D	0.486	neutral	N	0.466013187	None	None	N
E/C	0.7615	likely_pathogenic	0.7686	pathogenic	-0.349	Destabilizing	0.999	D	0.593	neutral	None	None	None	None	N
E/D	0.2725	likely_benign	0.2483	benign	-0.794	Destabilizing	0.959	D	0.49	neutral	N	0.520039027	None	None	N
E/F	0.7011	likely_pathogenic	0.6942	pathogenic	-0.225	Destabilizing	0.991	D	0.581	neutral	None	None	None	None	N
E/G	0.3245	likely_benign	0.2768	benign	-0.971	Destabilizing	0.959	D	0.547	neutral	N	0.482409148	None	None	N
E/H	0.4446	ambiguous	0.4256	ambiguous	-0.291	Destabilizing	0.991	D	0.566	neutral	None	None	None	None	N
E/I	0.2396	likely_benign	0.2367	benign	0.144	Stabilizing	0.884	D	0.6	neutral	None	None	None	None	N
E/K	0.148	likely_benign	0.1225	benign	-0.331	Destabilizing	0.134	N	0.172	neutral	N	0.453235245	None	None	N
E/L	0.3633	ambiguous	0.3457	ambiguous	0.144	Stabilizing	0.884	D	0.541	neutral	None	None	None	None	N
E/M	0.3686	ambiguous	0.3466	ambiguous	0.38	Stabilizing	0.991	D	0.574	neutral	None	None	None	None	N
E/N	0.373	ambiguous	0.3546	ambiguous	-0.74	Destabilizing	0.969	D	0.525	neutral	None	None	None	None	N
E/P	0.9787	likely_pathogenic	0.97	pathogenic	-0.105	Destabilizing	0.997	D	0.605	neutral	None	None	None	None	N
E/Q	0.1259	likely_benign	0.1192	benign	-0.638	Destabilizing	0.31	N	0.269	neutral	N	0.502759988	None	None	N
E/R	0.2432	likely_benign	0.2123	benign	-0.012	Destabilizing	0.046	N	0.305	neutral	None	None	None	None	N
E/S	0.2601	likely_benign	0.2436	benign	-0.97	Destabilizing	0.939	D	0.499	neutral	None	None	None	None	N
E/T	0.1993	likely_benign	0.1881	benign	-0.725	Destabilizing	0.939	D	0.533	neutral	None	None	None	None	N
E/V	0.1417	likely_benign	0.1354	benign	-0.105	Destabilizing	0.134	N	0.4	neutral	N	0.459894645	None	None	N
E/W	0.9141	likely_pathogenic	0.8996	pathogenic	0.003	Stabilizing	0.999	D	0.632	neutral	None	None	None	None	N
E/Y	0.6508	likely_pathogenic	0.6252	pathogenic	0.014	Stabilizing	0.997	D	0.581	neutral	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.