TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2912	8959;8960;8961	chr2:178769847;178769846;178769845	chr2:179634574;179634573;179634572
N2AB	2912	8959;8960;8961	chr2:178769847;178769846;178769845	chr2:179634574;179634573;179634572
N2A	2912	8959;8960;8961	chr2:178769847;178769846;178769845	chr2:179634574;179634573;179634572
N2B	2866	8821;8822;8823	chr2:178769847;178769846;178769845	chr2:179634574;179634573;179634572
Novex-1	2866	8821;8822;8823	chr2:178769847;178769846;178769845	chr2:179634574;179634573;179634572
Novex-2	2866	8821;8822;8823	chr2:178769847;178769846;178769845	chr2:179634574;179634573;179634572
Novex-3	2912	8959;8960;8961	chr2:178769847;178769846;178769845	chr2:179634574;179634573;179634572

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-19
• Domain position: 31
• Structural Position: 46
• Q(SASA): 0.1872
• 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
S/F	None	None	0.971	N	0.746	0.569	0.693576915185	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
S/A	0.0569	likely_benign	0.0546	benign	-0.719	Destabilizing	0.006	N	0.273	neutral	N	0.455608119	None	None	N
S/C	0.2467	likely_benign	0.2062	benign	-0.372	Destabilizing	0.992	D	0.722	prob.delet.	N	0.518417153	None	None	N
S/D	0.9847	likely_pathogenic	0.976	pathogenic	-0.677	Destabilizing	0.978	D	0.619	neutral	None	None	None	None	N
S/E	0.984	likely_pathogenic	0.9741	pathogenic	-0.594	Destabilizing	0.86	D	0.604	neutral	None	None	None	None	N
S/F	0.8946	likely_pathogenic	0.8156	pathogenic	-0.72	Destabilizing	0.971	D	0.746	deleterious	N	0.461663826	None	None	N
S/G	0.2866	likely_benign	0.2483	benign	-1.02	Destabilizing	0.559	D	0.588	neutral	None	None	None	None	N
S/H	0.9577	likely_pathogenic	0.942	pathogenic	-1.358	Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	N
S/I	0.8749	likely_pathogenic	0.7807	pathogenic	0.007	Stabilizing	0.956	D	0.719	prob.delet.	None	None	None	None	N
S/K	0.9968	likely_pathogenic	0.9944	pathogenic	-0.708	Destabilizing	0.86	D	0.596	neutral	None	None	None	None	N
S/L	0.595	likely_pathogenic	0.4789	ambiguous	0.007	Stabilizing	0.754	D	0.653	neutral	None	None	None	None	N
S/M	0.7769	likely_pathogenic	0.6839	pathogenic	0.008	Stabilizing	0.998	D	0.725	prob.delet.	None	None	None	None	N
S/N	0.9011	likely_pathogenic	0.8632	pathogenic	-0.809	Destabilizing	0.978	D	0.631	neutral	None	None	None	None	N
S/P	0.8511	likely_pathogenic	0.7773	pathogenic	-0.202	Destabilizing	0.971	D	0.716	prob.delet.	N	0.517278567	None	None	N
S/Q	0.9715	likely_pathogenic	0.957	pathogenic	-0.73	Destabilizing	0.978	D	0.676	prob.neutral	None	None	None	None	N
S/R	0.9914	likely_pathogenic	0.9874	pathogenic	-0.776	Destabilizing	0.956	D	0.721	prob.delet.	None	None	None	None	N
S/T	0.3333	likely_benign	0.2599	benign	-0.683	Destabilizing	0.822	D	0.585	neutral	N	0.501207226	None	None	N
S/V	0.6479	likely_pathogenic	0.5265	ambiguous	-0.202	Destabilizing	0.754	D	0.66	neutral	None	None	None	None	N
S/W	0.9643	likely_pathogenic	0.9369	pathogenic	-0.902	Destabilizing	0.998	D	0.748	deleterious	None	None	None	None	N
S/Y	0.882	likely_pathogenic	0.8053	pathogenic	-0.572	Destabilizing	0.99	D	0.751	deleterious	N	0.487535914	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.