TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18769	56530;56531;56532	chr2:178599596;178599595;178599594	chr2:179464323;179464322;179464321
N2AB	17128	51607;51608;51609	chr2:178599596;178599595;178599594	chr2:179464323;179464322;179464321
N2A	16201	48826;48827;48828	chr2:178599596;178599595;178599594	chr2:179464323;179464322;179464321
N2B	9704	29335;29336;29337	chr2:178599596;178599595;178599594	chr2:179464323;179464322;179464321
Novex-1	9829	29710;29711;29712	chr2:178599596;178599595;178599594	chr2:179464323;179464322;179464321
Novex-2	9896	29911;29912;29913	chr2:178599596;178599595;178599594	chr2:179464323;179464322;179464321
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-116
• Domain position: 82
• Structural Position: 162
• Q(SASA): 0.8963
• 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
N/D	None	None	0.961	N	0.432	0.29	0.280987212366	gnomAD-4.0.0	1.62984E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.92642E-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
N/A	0.1645	likely_benign	0.1454	benign	-0.093	Destabilizing	0.871	D	0.415	neutral	None	None	None	None	I
N/C	0.2508	likely_benign	0.2207	benign	0.154	Stabilizing	1.0	D	0.545	neutral	None	None	None	None	I
N/D	0.1524	likely_benign	0.1153	benign	0.079	Stabilizing	0.961	D	0.432	neutral	N	0.427449445	None	None	I
N/E	0.3892	ambiguous	0.2925	benign	0.016	Stabilizing	0.97	D	0.371	neutral	None	None	None	None	I
N/F	0.5193	ambiguous	0.457	ambiguous	-0.705	Destabilizing	0.999	D	0.54	neutral	None	None	None	None	I
N/G	0.2341	likely_benign	0.2021	benign	-0.184	Destabilizing	0.931	D	0.435	neutral	None	None	None	None	I
N/H	0.0981	likely_benign	0.0905	benign	-0.213	Destabilizing	0.998	D	0.417	neutral	N	0.451481098	None	None	I
N/I	0.1746	likely_benign	0.1544	benign	0.045	Stabilizing	0.994	D	0.531	neutral	N	0.435684926	None	None	I
N/K	0.3139	likely_benign	0.2366	benign	0.109	Stabilizing	0.961	D	0.373	neutral	N	0.418693889	None	None	I
N/L	0.2061	likely_benign	0.1843	benign	0.045	Stabilizing	0.985	D	0.439	neutral	None	None	None	None	I
N/M	0.3103	likely_benign	0.2886	benign	0.114	Stabilizing	1.0	D	0.528	neutral	None	None	None	None	I
N/P	0.3407	ambiguous	0.2834	benign	0.022	Stabilizing	0.996	D	0.495	neutral	None	None	None	None	I
N/Q	0.3056	likely_benign	0.2574	benign	-0.275	Destabilizing	0.996	D	0.384	neutral	None	None	None	None	I
N/R	0.3429	ambiguous	0.2637	benign	0.172	Stabilizing	0.996	D	0.367	neutral	None	None	None	None	I
N/S	0.0669	likely_benign	0.0647	benign	-0.042	Destabilizing	0.118	N	0.187	neutral	N	0.349639235	None	None	I
N/T	0.0977	likely_benign	0.0911	benign	0.007	Stabilizing	0.835	D	0.393	neutral	N	0.404553942	None	None	I
N/V	0.1788	likely_benign	0.1625	benign	0.022	Stabilizing	0.996	D	0.465	neutral	None	None	None	None	I
N/W	0.7921	likely_pathogenic	0.7342	pathogenic	-0.843	Destabilizing	1.0	D	0.638	neutral	None	None	None	None	I
N/Y	0.1853	likely_benign	0.1572	benign	-0.514	Destabilizing	0.998	D	0.527	neutral	N	0.451481098	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.