TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30496	91711;91712;91713	chr2:178551045;178551044;178551043	chr2:179415772;179415771;179415770
N2AB	28855	86788;86789;86790	chr2:178551045;178551044;178551043	chr2:179415772;179415771;179415770
N2A	27928	84007;84008;84009	chr2:178551045;178551044;178551043	chr2:179415772;179415771;179415770
N2B	21431	64516;64517;64518	chr2:178551045;178551044;178551043	chr2:179415772;179415771;179415770
Novex-1	21556	64891;64892;64893	chr2:178551045;178551044;178551043	chr2:179415772;179415771;179415770
Novex-2	21623	65092;65093;65094	chr2:178551045;178551044;178551043	chr2:179415772;179415771;179415770
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-110
• Domain position: 75
• Structural Position: 108
• Q(SASA): 0.0709
• 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	None	None	None	N	0.209	0.088	0.247322355667	gnomAD-4.0.0	1.59217E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8594E-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	0.7274	likely_pathogenic	0.7653	pathogenic	-3.103	Highly Destabilizing	0.157	N	0.633	neutral	None	None	None	None	N
I/C	0.8514	likely_pathogenic	0.874	pathogenic	-2.363	Highly Destabilizing	0.909	D	0.741	deleterious	None	None	None	None	N
I/D	0.9975	likely_pathogenic	0.998	pathogenic	-3.55	Highly Destabilizing	0.726	D	0.871	deleterious	None	None	None	None	N
I/E	0.9948	likely_pathogenic	0.9957	pathogenic	-3.241	Highly Destabilizing	0.726	D	0.861	deleterious	None	None	None	None	N
I/F	0.858	likely_pathogenic	0.8976	pathogenic	-1.69	Destabilizing	0.567	D	0.59	neutral	None	None	None	None	N
I/G	0.9721	likely_pathogenic	0.9779	pathogenic	-3.685	Highly Destabilizing	0.726	D	0.847	deleterious	None	None	None	None	N
I/H	0.9959	likely_pathogenic	0.9972	pathogenic	-3.129	Highly Destabilizing	0.968	D	0.875	deleterious	None	None	None	None	N
I/K	0.9945	likely_pathogenic	0.9954	pathogenic	-2.167	Highly Destabilizing	0.667	D	0.86	deleterious	N	0.496241578	None	None	N
I/L	0.3632	ambiguous	0.4024	ambiguous	-1.343	Destabilizing	0.025	N	0.276	neutral	N	0.462879022	None	None	N
I/M	0.393	ambiguous	0.4473	ambiguous	-1.678	Destabilizing	0.497	N	0.614	neutral	N	0.511617118	None	None	N
I/N	0.96	likely_pathogenic	0.9688	pathogenic	-2.8	Highly Destabilizing	0.89	D	0.884	deleterious	None	None	None	None	N
I/P	0.9925	likely_pathogenic	0.995	pathogenic	-1.923	Destabilizing	0.89	D	0.88	deleterious	None	None	None	None	N
I/Q	0.9926	likely_pathogenic	0.9941	pathogenic	-2.489	Highly Destabilizing	0.89	D	0.887	deleterious	None	None	None	None	N
I/R	0.9905	likely_pathogenic	0.9921	pathogenic	-2.122	Highly Destabilizing	0.667	D	0.88	deleterious	N	0.496241578	None	None	N
I/S	0.8988	likely_pathogenic	0.9182	pathogenic	-3.39	Highly Destabilizing	0.567	D	0.795	deleterious	None	None	None	None	N
I/T	0.8303	likely_pathogenic	0.8564	pathogenic	-2.927	Highly Destabilizing	0.124	N	0.659	neutral	N	0.478048418	None	None	N
I/V	0.0638	likely_benign	0.0712	benign	-1.923	Destabilizing	None	N	0.209	neutral	N	0.312535845	None	None	N
I/W	0.9984	likely_pathogenic	0.9989	pathogenic	-2.004	Highly Destabilizing	0.968	D	0.855	deleterious	None	None	None	None	N
I/Y	0.9889	likely_pathogenic	0.9922	pathogenic	-1.907	Destabilizing	0.726	D	0.718	prob.delet.	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.