TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16172	48739;48740;48741	chr2:178615431;178615430;178615429	chr2:179480158;179480157;179480156
N2AB	14531	43816;43817;43818	chr2:178615431;178615430;178615429	chr2:179480158;179480157;179480156
N2A	13604	41035;41036;41037	chr2:178615431;178615430;178615429	chr2:179480158;179480157;179480156
N2B	7107	21544;21545;21546	chr2:178615431;178615430;178615429	chr2:179480158;179480157;179480156
Novex-1	7232	21919;21920;21921	chr2:178615431;178615430;178615429	chr2:179480158;179480157;179480156
Novex-2	7299	22120;22121;22122	chr2:178615431;178615430;178615429	chr2:179480158;179480157;179480156
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-5
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0781
• 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
I/N	None	None	1.0	D	0.884	0.646	0.864374381892	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
I/A	0.9172	likely_pathogenic	0.9303	pathogenic	-2.661	Highly Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
I/C	0.9259	likely_pathogenic	0.941	pathogenic	-1.682	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
I/D	0.9993	likely_pathogenic	0.9992	pathogenic	-3.157	Highly Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
I/E	0.9985	likely_pathogenic	0.9984	pathogenic	-2.815	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
I/F	0.7902	likely_pathogenic	0.8334	pathogenic	-1.526	Destabilizing	1.0	D	0.785	deleterious	D	0.587348933	None	None	N
I/G	0.9943	likely_pathogenic	0.9954	pathogenic	-3.291	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
I/H	0.9959	likely_pathogenic	0.996	pathogenic	-3.047	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
I/K	0.9968	likely_pathogenic	0.9965	pathogenic	-1.776	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
I/L	0.3528	ambiguous	0.3814	ambiguous	-0.755	Destabilizing	0.993	D	0.347	neutral	N	0.462928373	None	None	N
I/M	0.5171	ambiguous	0.572	pathogenic	-0.981	Destabilizing	1.0	D	0.777	deleterious	N	0.476383085	None	None	N
I/N	0.988	likely_pathogenic	0.9883	pathogenic	-2.526	Highly Destabilizing	1.0	D	0.884	deleterious	D	0.694307044	None	None	N
I/P	0.9977	likely_pathogenic	0.9972	pathogenic	-1.383	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
I/Q	0.9956	likely_pathogenic	0.9954	pathogenic	-2.111	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
I/R	0.9928	likely_pathogenic	0.9922	pathogenic	-2.004	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
I/S	0.9745	likely_pathogenic	0.9759	pathogenic	-3.067	Highly Destabilizing	1.0	D	0.833	deleterious	D	0.60260908	None	None	N
I/T	0.9564	likely_pathogenic	0.963	pathogenic	-2.55	Highly Destabilizing	1.0	D	0.809	deleterious	D	0.602008645	None	None	N
I/V	0.1271	likely_benign	0.1409	benign	-1.383	Destabilizing	0.993	D	0.292	neutral	N	0.410070217	None	None	N
I/W	0.9975	likely_pathogenic	0.9975	pathogenic	-1.864	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
I/Y	0.9806	likely_pathogenic	0.9814	pathogenic	-1.684	Destabilizing	1.0	D	0.851	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.