TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20951	63076;63077;63078	chr2:178588874;178588873;178588872	chr2:179453601;179453600;179453599
N2AB	19310	58153;58154;58155	chr2:178588874;178588873;178588872	chr2:179453601;179453600;179453599
N2A	18383	55372;55373;55374	chr2:178588874;178588873;178588872	chr2:179453601;179453600;179453599
N2B	11886	35881;35882;35883	chr2:178588874;178588873;178588872	chr2:179453601;179453600;179453599
Novex-1	12011	36256;36257;36258	chr2:178588874;178588873;178588872	chr2:179453601;179453600;179453599
Novex-2	12078	36457;36458;36459	chr2:178588874;178588873;178588872	chr2:179453601;179453600;179453599
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: Fn3-39
• Domain position: 88
• Structural Position: 122
• Q(SASA): 0.3517
• 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	0.999	N	0.8	0.228	0.512998934155	gnomAD-4.0.0	4.79083E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	8.11632E-05	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	0.3312	likely_benign	0.2577	benign	-0.715	Destabilizing	0.997	D	0.787	deleterious	D	0.530883244	None	None	N
E/C	0.9394	likely_pathogenic	0.9121	pathogenic	-0.371	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/D	0.2961	likely_benign	0.2706	benign	-0.794	Destabilizing	0.997	D	0.761	deleterious	D	0.531344604	None	None	N
E/F	0.8802	likely_pathogenic	0.815	pathogenic	0.073	Stabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
E/G	0.5934	likely_pathogenic	0.4751	ambiguous	-1.071	Destabilizing	0.999	D	0.727	deleterious	N	0.493859538	None	None	N
E/H	0.8231	likely_pathogenic	0.7301	pathogenic	0.086	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
E/I	0.4087	ambiguous	0.3096	benign	0.252	Stabilizing	0.999	D	0.828	deleterious	None	None	None	None	N
E/K	0.4929	ambiguous	0.302	benign	-0.103	Destabilizing	0.997	D	0.821	deleterious	N	0.485083672	None	None	N
E/L	0.5591	ambiguous	0.447	ambiguous	0.252	Stabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
E/M	0.6062	likely_pathogenic	0.5003	ambiguous	0.495	Stabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
E/N	0.5913	likely_pathogenic	0.4949	ambiguous	-0.812	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
E/P	0.7496	likely_pathogenic	0.7392	pathogenic	-0.049	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
E/Q	0.2982	likely_benign	0.2227	benign	-0.663	Destabilizing	0.999	D	0.8	deleterious	N	0.512662842	None	None	N
E/R	0.6882	likely_pathogenic	0.5133	ambiguous	0.267	Stabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
E/S	0.4758	ambiguous	0.3914	ambiguous	-1.06	Destabilizing	0.998	D	0.806	deleterious	None	None	None	None	N
E/T	0.3864	ambiguous	0.3028	benign	-0.745	Destabilizing	0.999	D	0.742	deleterious	None	None	None	None	N
E/V	0.2519	likely_benign	0.1827	benign	-0.049	Destabilizing	0.999	D	0.769	deleterious	N	0.492960938	None	None	N
E/W	0.976	likely_pathogenic	0.9573	pathogenic	0.44	Stabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/Y	0.8452	likely_pathogenic	0.7508	pathogenic	0.383	Stabilizing	1.0	D	0.857	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.