TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20110	60553;60554;60555	chr2:178591397;178591396;178591395	chr2:179456124;179456123;179456122
N2AB	18469	55630;55631;55632	chr2:178591397;178591396;178591395	chr2:179456124;179456123;179456122
N2A	17542	52849;52850;52851	chr2:178591397;178591396;178591395	chr2:179456124;179456123;179456122
N2B	11045	33358;33359;33360	chr2:178591397;178591396;178591395	chr2:179456124;179456123;179456122
Novex-1	11170	33733;33734;33735	chr2:178591397;178591396;178591395	chr2:179456124;179456123;179456122
Novex-2	11237	33934;33935;33936	chr2:178591397;178591396;178591395	chr2:179456124;179456123;179456122
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-120
• Domain position: 31
• Structural Position: 46
• Q(SASA): 0.2825
• Predicted PPI site: I

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
A/G	None	None	0.787	N	0.669	0.189	0.336155897331	gnomAD-4.0.0	4.78042E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.58512E-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
A/C	0.4541	ambiguous	0.4397	ambiguous	-0.786	Destabilizing	0.985	D	0.699	prob.neutral	None	None	None	None	I
A/D	0.8663	likely_pathogenic	0.8941	pathogenic	-0.654	Destabilizing	0.945	D	0.832	deleterious	None	None	None	None	I
A/E	0.7385	likely_pathogenic	0.7805	pathogenic	-0.711	Destabilizing	0.928	D	0.746	deleterious	N	0.500367225	None	None	I
A/F	0.5655	likely_pathogenic	0.6008	pathogenic	-0.928	Destabilizing	0.894	D	0.838	deleterious	None	None	None	None	I
A/G	0.2505	likely_benign	0.2638	benign	-0.946	Destabilizing	0.787	D	0.669	neutral	N	0.488846335	None	None	I
A/H	0.8315	likely_pathogenic	0.8555	pathogenic	-1.128	Destabilizing	0.995	D	0.807	deleterious	None	None	None	None	I
A/I	0.2042	likely_benign	0.1951	benign	-0.265	Destabilizing	0.593	D	0.752	deleterious	None	None	None	None	I
A/K	0.8236	likely_pathogenic	0.861	pathogenic	-0.962	Destabilizing	0.945	D	0.739	prob.delet.	None	None	None	None	I
A/L	0.2698	likely_benign	0.2954	benign	-0.265	Destabilizing	0.547	D	0.723	prob.delet.	None	None	None	None	I
A/M	0.3139	likely_benign	0.3114	benign	-0.243	Destabilizing	0.97	D	0.721	prob.delet.	None	None	None	None	I
A/N	0.6845	likely_pathogenic	0.7194	pathogenic	-0.625	Destabilizing	0.981	D	0.831	deleterious	None	None	None	None	I
A/P	0.3119	likely_benign	0.3249	benign	-0.374	Destabilizing	0.013	N	0.526	neutral	N	0.488846335	None	None	I
A/Q	0.7011	likely_pathogenic	0.7324	pathogenic	-0.785	Destabilizing	0.981	D	0.725	prob.delet.	None	None	None	None	I
A/R	0.7781	likely_pathogenic	0.8183	pathogenic	-0.659	Destabilizing	0.945	D	0.732	prob.delet.	None	None	None	None	I
A/S	0.1515	likely_benign	0.1515	benign	-0.995	Destabilizing	0.645	D	0.673	neutral	N	0.494039796	None	None	I
A/T	0.1042	likely_benign	0.1081	benign	-0.95	Destabilizing	0.645	D	0.689	prob.neutral	N	0.481745289	None	None	I
A/V	0.0925	likely_benign	0.0869	benign	-0.374	Destabilizing	0.013	N	0.429	neutral	N	0.367155055	None	None	I
A/W	0.9133	likely_pathogenic	0.923	pathogenic	-1.228	Destabilizing	0.995	D	0.793	deleterious	None	None	None	None	I
A/Y	0.7558	likely_pathogenic	0.7764	pathogenic	-0.82	Destabilizing	0.945	D	0.84	deleterious	None	None	None	None	I

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.