TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27805	83638;83639;83640	chr2:178562719;178562718;178562717	chr2:179427446;179427445;179427444
N2AB	26164	78715;78716;78717	chr2:178562719;178562718;178562717	chr2:179427446;179427445;179427444
N2A	25237	75934;75935;75936	chr2:178562719;178562718;178562717	chr2:179427446;179427445;179427444
N2B	18740	56443;56444;56445	chr2:178562719;178562718;178562717	chr2:179427446;179427445;179427444
Novex-1	18865	56818;56819;56820	chr2:178562719;178562718;178562717	chr2:179427446;179427445;179427444
Novex-2	18932	57019;57020;57021	chr2:178562719;178562718;178562717	chr2:179427446;179427445;179427444
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-90
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.2326
• 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
K/N	rs774475131	-2.02	0.998	N	0.769	0.342	0.233785782151	gnomAD-2.1.1	4.18E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.6E-05	None	0	0	0
K/N	rs774475131	-2.02	0.998	N	0.769	0.342	0.233785782151	gnomAD-4.0.0	1.62829E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.49638E-05	0
K/R	rs1215650714	-0.525	0.961	N	0.681	0.316	0.38342384377	gnomAD-2.1.1	4.18E-06	None	None	None	None	N	None	6.54E-05	0	None	0	0	None	0	None	0	0	0
K/R	rs1215650714	-0.525	0.961	N	0.681	0.316	0.38342384377	gnomAD-4.0.0	1.62705E-06	None	None	None	None	N	None	5.94884E-05	0	None	0	0	None	0	0	0	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
K/A	0.9713	likely_pathogenic	0.9681	pathogenic	-1.361	Destabilizing	0.989	D	0.665	neutral	None	None	None	None	N
K/C	0.9293	likely_pathogenic	0.9121	pathogenic	-1.386	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
K/D	0.998	likely_pathogenic	0.998	pathogenic	-1.923	Destabilizing	0.999	D	0.776	deleterious	None	None	None	None	N
K/E	0.9544	likely_pathogenic	0.9517	pathogenic	-1.606	Destabilizing	0.976	D	0.693	prob.neutral	N	0.515161391	None	None	N
K/F	0.9873	likely_pathogenic	0.9849	pathogenic	-0.717	Destabilizing	0.984	D	0.817	deleterious	None	None	None	None	N
K/G	0.9787	likely_pathogenic	0.9748	pathogenic	-1.843	Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
K/H	0.8703	likely_pathogenic	0.8546	pathogenic	-1.441	Destabilizing	0.992	D	0.803	deleterious	None	None	None	None	N
K/I	0.9094	likely_pathogenic	0.9284	pathogenic	0.015	Stabilizing	0.873	D	0.829	deleterious	N	0.466391581	None	None	N
K/L	0.8874	likely_pathogenic	0.8877	pathogenic	0.015	Stabilizing	0.564	D	0.741	deleterious	None	None	None	None	N
K/M	0.7424	likely_pathogenic	0.729	pathogenic	-0.347	Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	N
K/N	0.9875	likely_pathogenic	0.9867	pathogenic	-1.785	Destabilizing	0.998	D	0.769	deleterious	N	0.521909341	None	None	N
K/P	0.9993	likely_pathogenic	0.9994	pathogenic	-0.426	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
K/Q	0.6478	likely_pathogenic	0.622	pathogenic	-1.414	Destabilizing	0.983	D	0.776	deleterious	N	0.493930038	None	None	N
K/R	0.1741	likely_benign	0.1593	benign	-0.609	Destabilizing	0.961	D	0.681	prob.neutral	N	0.50083719	None	None	N
K/S	0.9839	likely_pathogenic	0.9796	pathogenic	-2.333	Highly Destabilizing	0.994	D	0.687	prob.neutral	None	None	None	None	N
K/T	0.9262	likely_pathogenic	0.9247	pathogenic	-1.744	Destabilizing	0.993	D	0.735	prob.delet.	N	0.500068876	None	None	N
K/V	0.8905	likely_pathogenic	0.8998	pathogenic	-0.426	Destabilizing	0.923	D	0.761	deleterious	None	None	None	None	N
K/W	0.9796	likely_pathogenic	0.9771	pathogenic	-0.725	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
K/Y	0.9412	likely_pathogenic	0.9298	pathogenic	-0.385	Destabilizing	0.029	N	0.578	neutral	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.