TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23570	70933;70934;70935	chr2:178575424;178575423;178575422	chr2:179440151;179440150;179440149
N2AB	21929	66010;66011;66012	chr2:178575424;178575423;178575422	chr2:179440151;179440150;179440149
N2A	21002	63229;63230;63231	chr2:178575424;178575423;178575422	chr2:179440151;179440150;179440149
N2B	14505	43738;43739;43740	chr2:178575424;178575423;178575422	chr2:179440151;179440150;179440149
Novex-1	14630	44113;44114;44115	chr2:178575424;178575423;178575422	chr2:179440151;179440150;179440149
Novex-2	14697	44314;44315;44316	chr2:178575424;178575423;178575422	chr2:179440151;179440150;179440149
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: Fn3-59
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.1504
• 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/K	None	None	1.0	N	0.678	0.433	0.347879110917	gnomAD-4.0.0	1.59174E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85935E-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	0.4701	ambiguous	0.503	ambiguous	-2.712	Highly Destabilizing	1.0	D	0.686	prob.neutral	D	0.536837272	None	None	N
E/C	0.9556	likely_pathogenic	0.9585	pathogenic	-1.742	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/D	0.7138	likely_pathogenic	0.7295	pathogenic	-1.808	Destabilizing	0.998	D	0.623	neutral	N	0.480967571	None	None	N
E/F	0.9645	likely_pathogenic	0.969	pathogenic	-2.375	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
E/G	0.7016	likely_pathogenic	0.726	pathogenic	-3.048	Highly Destabilizing	1.0	D	0.77	deleterious	D	0.531863749	None	None	N
E/H	0.8812	likely_pathogenic	0.8888	pathogenic	-2.212	Highly Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
E/I	0.8336	likely_pathogenic	0.8531	pathogenic	-1.718	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
E/K	0.6334	likely_pathogenic	0.6493	pathogenic	-2.687	Highly Destabilizing	1.0	D	0.678	prob.neutral	N	0.495905048	None	None	N
E/L	0.814	likely_pathogenic	0.836	pathogenic	-1.718	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/M	0.7927	likely_pathogenic	0.8197	pathogenic	-0.852	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
E/N	0.8064	likely_pathogenic	0.8285	pathogenic	-2.648	Highly Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
E/P	0.9983	likely_pathogenic	0.9987	pathogenic	-2.042	Highly Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/Q	0.3431	ambiguous	0.3524	ambiguous	-2.375	Highly Destabilizing	1.0	D	0.731	prob.delet.	N	0.473508378	None	None	N
E/R	0.7559	likely_pathogenic	0.7638	pathogenic	-2.322	Highly Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
E/S	0.5723	likely_pathogenic	0.6089	pathogenic	-3.429	Highly Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
E/T	0.6779	likely_pathogenic	0.709	pathogenic	-3.11	Highly Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/V	0.6348	likely_pathogenic	0.6676	pathogenic	-2.042	Highly Destabilizing	1.0	D	0.782	deleterious	N	0.519493486	None	None	N
E/W	0.991	likely_pathogenic	0.9912	pathogenic	-2.39	Highly Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
E/Y	0.9479	likely_pathogenic	0.9544	pathogenic	-2.282	Highly Destabilizing	1.0	D	0.83	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.