TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24362	73309;73310;73311	chr2:178573048;178573047;178573046	chr2:179437775;179437774;179437773
N2AB	22721	68386;68387;68388	chr2:178573048;178573047;178573046	chr2:179437775;179437774;179437773
N2A	21794	65605;65606;65607	chr2:178573048;178573047;178573046	chr2:179437775;179437774;179437773
N2B	15297	46114;46115;46116	chr2:178573048;178573047;178573046	chr2:179437775;179437774;179437773
Novex-1	15422	46489;46490;46491	chr2:178573048;178573047;178573046	chr2:179437775;179437774;179437773
Novex-2	15489	46690;46691;46692	chr2:178573048;178573047;178573046	chr2:179437775;179437774;179437773
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: Fn3-65
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.116
• 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/T	rs1708819361	None	0.004	N	0.466	0.232	0.498896430806	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/T	rs1708819361	None	0.004	N	0.466	0.232	0.498896430806	gnomAD-4.0.0	3.0452E-06	None	None	None	None	N	None	1.74825E-05	0	None	0	0	None	0	5.16529E-04	1.20498E-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	0.2759	likely_benign	0.2452	benign	-2.323	Highly Destabilizing	0.373	N	0.645	neutral	None	None	None	None	N
I/C	0.6679	likely_pathogenic	0.6588	pathogenic	-1.435	Destabilizing	0.009	N	0.575	neutral	None	None	None	None	N
I/D	0.9208	likely_pathogenic	0.8983	pathogenic	-2.845	Highly Destabilizing	0.854	D	0.789	deleterious	None	None	None	None	N
I/E	0.7731	likely_pathogenic	0.7435	pathogenic	-2.545	Highly Destabilizing	0.854	D	0.788	deleterious	None	None	None	None	N
I/F	0.1894	likely_benign	0.1807	benign	-1.339	Destabilizing	0.939	D	0.759	deleterious	N	0.469783565	None	None	N
I/G	0.7946	likely_pathogenic	0.748	pathogenic	-2.924	Highly Destabilizing	0.854	D	0.751	deleterious	None	None	None	None	N
I/H	0.6303	likely_pathogenic	0.6125	pathogenic	-2.571	Highly Destabilizing	0.996	D	0.771	deleterious	None	None	None	None	N
I/K	0.3082	likely_benign	0.3156	benign	-1.71	Destabilizing	0.742	D	0.781	deleterious	None	None	None	None	N
I/L	0.1222	likely_benign	0.1165	benign	-0.547	Destabilizing	0.164	N	0.393	neutral	N	0.467665979	None	None	N
I/M	0.0692	likely_benign	0.0696	benign	-0.568	Destabilizing	0.979	D	0.737	prob.delet.	N	0.421531045	None	None	N
I/N	0.5942	likely_pathogenic	0.5282	ambiguous	-2.301	Highly Destabilizing	0.939	D	0.793	deleterious	N	0.518134872	None	None	N
I/P	0.9778	likely_pathogenic	0.9701	pathogenic	-1.124	Destabilizing	0.984	D	0.795	deleterious	None	None	None	None	N
I/Q	0.5521	ambiguous	0.5363	ambiguous	-2.004	Highly Destabilizing	0.984	D	0.784	deleterious	None	None	None	None	N
I/R	0.2917	likely_benign	0.2811	benign	-1.717	Destabilizing	0.953	D	0.791	deleterious	None	None	None	None	N
I/S	0.4166	ambiguous	0.3643	ambiguous	-2.931	Highly Destabilizing	0.309	N	0.707	prob.neutral	N	0.482059429	None	None	N
I/T	0.1332	likely_benign	0.1217	benign	-2.467	Highly Destabilizing	0.004	N	0.466	neutral	N	0.452256597	None	None	N
I/V	0.0805	likely_benign	0.0816	benign	-1.124	Destabilizing	0.281	N	0.376	neutral	N	0.431937253	None	None	N
I/W	0.7718	likely_pathogenic	0.7581	pathogenic	-1.797	Destabilizing	0.996	D	0.765	deleterious	None	None	None	None	N
I/Y	0.5087	ambiguous	0.4721	ambiguous	-1.453	Destabilizing	0.984	D	0.799	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.