TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20285	61078;61079;61080	chr2:178590872;178590871;178590870	chr2:179455599;179455598;179455597
N2AB	18644	56155;56156;56157	chr2:178590872;178590871;178590870	chr2:179455599;179455598;179455597
N2A	17717	53374;53375;53376	chr2:178590872;178590871;178590870	chr2:179455599;179455598;179455597
N2B	11220	33883;33884;33885	chr2:178590872;178590871;178590870	chr2:179455599;179455598;179455597
Novex-1	11345	34258;34259;34260	chr2:178590872;178590871;178590870	chr2:179455599;179455598;179455597
Novex-2	11412	34459;34460;34461	chr2:178590872;178590871;178590870	chr2:179455599;179455598;179455597
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: Fn3-35
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.3213
• 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	rs1362658901	None	0.999	N	0.584	0.431	0.289847578895	gnomAD-4.0.0	2.05795E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.70578E-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	0.2409	likely_benign	0.2905	benign	-0.313	Destabilizing	0.999	D	0.625	neutral	N	0.440866167	None	None	N
E/C	0.9288	likely_pathogenic	0.9465	pathogenic	0.161	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/D	0.2606	likely_benign	0.3176	benign	-0.683	Destabilizing	0.999	D	0.445	neutral	N	0.454392825	None	None	N
E/F	0.9568	likely_pathogenic	0.9687	pathogenic	-0.564	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/G	0.2688	likely_benign	0.3277	benign	-0.537	Destabilizing	1.0	D	0.692	prob.neutral	N	0.465340537	None	None	N
E/H	0.7936	likely_pathogenic	0.8328	pathogenic	-0.779	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/I	0.7601	likely_pathogenic	0.8036	pathogenic	0.243	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
E/K	0.3782	ambiguous	0.4177	ambiguous	0.13	Stabilizing	0.999	D	0.584	neutral	N	0.399424976	None	None	N
E/L	0.8054	likely_pathogenic	0.8448	pathogenic	0.243	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
E/M	0.794	likely_pathogenic	0.8297	pathogenic	0.59	Stabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
E/N	0.5685	likely_pathogenic	0.6425	pathogenic	-0.012	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/P	0.6934	likely_pathogenic	0.7387	pathogenic	0.08	Stabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
E/Q	0.2836	likely_benign	0.3125	benign	-0.008	Destabilizing	1.0	D	0.666	neutral	N	0.504725645	None	None	N
E/R	0.5714	likely_pathogenic	0.6207	pathogenic	0.115	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/S	0.3483	ambiguous	0.4162	ambiguous	-0.204	Destabilizing	0.999	D	0.69	prob.neutral	None	None	None	None	N
E/T	0.5585	ambiguous	0.6218	pathogenic	-0.037	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
E/V	0.5382	ambiguous	0.5989	pathogenic	0.08	Stabilizing	1.0	D	0.729	prob.delet.	N	0.480246782	None	None	N
E/W	0.9748	likely_pathogenic	0.9825	pathogenic	-0.569	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/Y	0.8856	likely_pathogenic	0.9196	pathogenic	-0.354	Destabilizing	1.0	D	0.741	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.