TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34442	103549;103550;103551	chr2:178533291;178533290;178533289	chr2:179398018;179398017;179398016
N2AB	32801	98626;98627;98628	chr2:178533291;178533290;178533289	chr2:179398018;179398017;179398016
N2A	31874	95845;95846;95847	chr2:178533291;178533290;178533289	chr2:179398018;179398017;179398016
N2B	25377	76354;76355;76356	chr2:178533291;178533290;178533289	chr2:179398018;179398017;179398016
Novex-1	25502	76729;76730;76731	chr2:178533291;178533290;178533289	chr2:179398018;179398017;179398016
Novex-2	25569	76930;76931;76932	chr2:178533291;178533290;178533289	chr2:179398018;179398017;179398016
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-162
• Domain position: 80
• Structural Position: 163
• Q(SASA): 0.6057
• 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/V	rs745548644	-0.039	1.0	N	0.659	0.419	0.541376754579	gnomAD-2.1.1	2.81E-05	None	None	None	None	I	None	0	0	None	0	0	None	2.28743E-04	None	0	0	0
A/V	rs745548644	-0.039	1.0	N	0.659	0.419	0.541376754579	gnomAD-4.0.0	1.09465E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.8549E-04	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	0.8348	likely_pathogenic	0.7954	pathogenic	-0.805	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
A/D	0.9412	likely_pathogenic	0.9111	pathogenic	-0.49	Destabilizing	1.0	D	0.784	deleterious	N	0.513221695	None	None	I
A/E	0.8818	likely_pathogenic	0.8031	pathogenic	-0.648	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	I
A/F	0.7613	likely_pathogenic	0.6674	pathogenic	-0.907	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
A/G	0.6226	likely_pathogenic	0.5496	ambiguous	-0.22	Destabilizing	1.0	D	0.591	neutral	D	0.531520749	None	None	I
A/H	0.878	likely_pathogenic	0.8356	pathogenic	-0.22	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
A/I	0.771	likely_pathogenic	0.6288	pathogenic	-0.385	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
A/K	0.9516	likely_pathogenic	0.9048	pathogenic	-0.523	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
A/L	0.6679	likely_pathogenic	0.5667	pathogenic	-0.385	Destabilizing	1.0	D	0.66	neutral	None	None	None	None	I
A/M	0.7175	likely_pathogenic	0.5741	pathogenic	-0.468	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	I
A/N	0.8603	likely_pathogenic	0.8081	pathogenic	-0.237	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
A/P	0.9759	likely_pathogenic	0.9746	pathogenic	-0.3	Destabilizing	1.0	D	0.719	prob.delet.	D	0.53132595	None	None	I
A/Q	0.8396	likely_pathogenic	0.7624	pathogenic	-0.516	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	I
A/R	0.8935	likely_pathogenic	0.8224	pathogenic	-0.07	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
A/S	0.2345	likely_benign	0.2018	benign	-0.419	Destabilizing	1.0	D	0.629	neutral	N	0.51986096	None	None	I
A/T	0.4569	ambiguous	0.3234	benign	-0.503	Destabilizing	1.0	D	0.7	prob.neutral	N	0.498405442	None	None	I
A/V	0.428	ambiguous	0.289	benign	-0.3	Destabilizing	1.0	D	0.659	neutral	N	0.473221807	None	None	I
A/W	0.9726	likely_pathogenic	0.9587	pathogenic	-1.013	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	I
A/Y	0.8878	likely_pathogenic	0.845	pathogenic	-0.684	Destabilizing	1.0	D	0.779	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.