TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35774	107545;107546;107547	chr2:178528331;178528330;178528329	chr2:179393058;179393057;179393056
N2AB	34133	102622;102623;102624	chr2:178528331;178528330;178528329	chr2:179393058;179393057;179393056
N2A	33206	99841;99842;99843	chr2:178528331;178528330;178528329	chr2:179393058;179393057;179393056
N2B	26709	80350;80351;80352	chr2:178528331;178528330;178528329	chr2:179393058;179393057;179393056
Novex-1	26834	80725;80726;80727	chr2:178528331;178528330;178528329	chr2:179393058;179393057;179393056
Novex-2	26901	80926;80927;80928	chr2:178528331;178528330;178528329	chr2:179393058;179393057;179393056
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: Ig-168
• Domain position: 73
• Structural Position: 156
• Q(SASA): 0.0624
• 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	rs774401824	-1.068	None	N	0.326	0.113	0.132336055621	gnomAD-2.1.1	4.01E-05	None	None	None	None	N	None	0	0	None	0	5.56545E-04	None	0	None	0	0	0
I/V	rs774401824	-1.068	None	N	0.326	0.113	0.132336055621	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.9216E-04	None	0	0	0	0	0
I/V	rs774401824	-1.068	None	N	0.326	0.113	0.132336055621	gnomAD-4.0.0	6.19629E-06	None	None	None	None	N	None	0	0	None	0	2.00463E-04	None	0	0	8.47548E-07	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	0.8474	likely_pathogenic	0.8257	pathogenic	-2.549	Highly Destabilizing	0.072	N	0.723	prob.delet.	None	None	None	None	N
I/C	0.9387	likely_pathogenic	0.9351	pathogenic	-1.747	Destabilizing	0.909	D	0.79	deleterious	None	None	None	None	N
I/D	0.9983	likely_pathogenic	0.998	pathogenic	-3.038	Highly Destabilizing	0.726	D	0.848	deleterious	None	None	None	None	N
I/E	0.9938	likely_pathogenic	0.992	pathogenic	-2.741	Highly Destabilizing	0.726	D	0.833	deleterious	None	None	None	None	N
I/F	0.6965	likely_pathogenic	0.6735	pathogenic	-1.482	Destabilizing	0.497	N	0.7	prob.neutral	N	0.494612146	None	None	N
I/G	0.9826	likely_pathogenic	0.9792	pathogenic	-3.16	Highly Destabilizing	0.726	D	0.824	deleterious	None	None	None	None	N
I/H	0.9951	likely_pathogenic	0.9941	pathogenic	-2.769	Highly Destabilizing	0.968	D	0.865	deleterious	None	None	None	None	N
I/K	0.9919	likely_pathogenic	0.9893	pathogenic	-1.816	Destabilizing	0.726	D	0.836	deleterious	None	None	None	None	N
I/L	0.2835	likely_benign	0.2746	benign	-0.74	Destabilizing	0.025	N	0.395	neutral	N	0.430656668	None	None	N
I/M	0.3201	likely_benign	0.3107	benign	-0.788	Destabilizing	0.497	N	0.67	neutral	N	0.49530558	None	None	N
I/N	0.9789	likely_pathogenic	0.9756	pathogenic	-2.374	Highly Destabilizing	0.859	D	0.85	deleterious	N	0.495652296	None	None	N
I/P	0.996	likely_pathogenic	0.9957	pathogenic	-1.33	Destabilizing	0.726	D	0.852	deleterious	None	None	None	None	N
I/Q	0.9894	likely_pathogenic	0.9874	pathogenic	-2.098	Highly Destabilizing	0.89	D	0.851	deleterious	None	None	None	None	N
I/R	0.985	likely_pathogenic	0.9805	pathogenic	-1.793	Destabilizing	0.726	D	0.849	deleterious	None	None	None	None	N
I/S	0.9546	likely_pathogenic	0.9462	pathogenic	-3.044	Highly Destabilizing	0.497	N	0.793	deleterious	N	0.476623818	None	None	N
I/T	0.9114	likely_pathogenic	0.9009	pathogenic	-2.582	Highly Destabilizing	0.124	N	0.721	prob.delet.	N	0.47645046	None	None	N
I/V	0.0697	likely_benign	0.0713	benign	-1.33	Destabilizing	None	N	0.326	neutral	N	0.373205875	None	None	N
I/W	0.9944	likely_pathogenic	0.9934	pathogenic	-1.925	Destabilizing	0.968	D	0.854	deleterious	None	None	None	None	N
I/Y	0.9726	likely_pathogenic	0.9682	pathogenic	-1.631	Destabilizing	0.726	D	0.777	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.