TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21456	64591;64592;64593	chr2:178586535;178586534;178586533	chr2:179451262;179451261;179451260
N2AB	19815	59668;59669;59670	chr2:178586535;178586534;178586533	chr2:179451262;179451261;179451260
N2A	18888	56887;56888;56889	chr2:178586535;178586534;178586533	chr2:179451262;179451261;179451260
N2B	12391	37396;37397;37398	chr2:178586535;178586534;178586533	chr2:179451262;179451261;179451260
Novex-1	12516	37771;37772;37773	chr2:178586535;178586534;178586533	chr2:179451262;179451261;179451260
Novex-2	12583	37972;37973;37974	chr2:178586535;178586534;178586533	chr2:179451262;179451261;179451260
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: Fn3-43
• Domain position: 91
• Structural Position: 124
• Q(SASA): 0.6528
• 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
E/K	rs1432709459	None	0.457	N	0.521	0.183	0.250039746154	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-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
E/A	0.2048	likely_benign	0.1468	benign	0.036	Stabilizing	0.297	N	0.535	neutral	N	0.451438238	None	None	I
E/C	0.9216	likely_pathogenic	0.8575	pathogenic	-0.236	Destabilizing	0.989	D	0.787	deleterious	None	None	None	None	I
E/D	0.132	likely_benign	0.1041	benign	-0.331	Destabilizing	0.003	N	0.218	neutral	N	0.473064304	None	None	I
E/F	0.8843	likely_pathogenic	0.798	pathogenic	-0.041	Destabilizing	0.888	D	0.769	deleterious	None	None	None	None	I
E/G	0.2665	likely_benign	0.191	benign	-0.057	Destabilizing	0.457	N	0.491	neutral	N	0.480030349	None	None	I
E/H	0.6783	likely_pathogenic	0.5192	ambiguous	0.606	Stabilizing	0.989	D	0.577	neutral	None	None	None	None	I
E/I	0.5685	likely_pathogenic	0.425	ambiguous	0.22	Stabilizing	0.797	D	0.784	deleterious	None	None	None	None	I
E/K	0.3262	likely_benign	0.2087	benign	0.38	Stabilizing	0.457	N	0.521	neutral	N	0.486454889	None	None	I
E/L	0.5951	likely_pathogenic	0.4501	ambiguous	0.22	Stabilizing	0.662	D	0.562	neutral	None	None	None	None	I
E/M	0.6859	likely_pathogenic	0.5503	ambiguous	-0.041	Destabilizing	0.989	D	0.736	deleterious	None	None	None	None	I
E/N	0.4047	ambiguous	0.2676	benign	0.187	Stabilizing	0.662	D	0.508	neutral	None	None	None	None	I
E/P	0.4641	ambiguous	0.365	ambiguous	0.175	Stabilizing	0.888	D	0.597	neutral	None	None	None	None	I
E/Q	0.2689	likely_benign	0.1886	benign	0.185	Stabilizing	0.747	D	0.531	neutral	N	0.497922676	None	None	I
E/R	0.4858	ambiguous	0.3461	ambiguous	0.599	Stabilizing	0.797	D	0.579	neutral	None	None	None	None	I
E/S	0.2672	likely_benign	0.1838	benign	0.04	Stabilizing	0.359	N	0.451	neutral	None	None	None	None	I
E/T	0.3083	likely_benign	0.216	benign	0.126	Stabilizing	0.033	N	0.411	neutral	None	None	None	None	I
E/V	0.3526	ambiguous	0.2526	benign	0.175	Stabilizing	0.597	D	0.485	neutral	N	0.45930836	None	None	I
E/W	0.951	likely_pathogenic	0.9073	pathogenic	-0.018	Destabilizing	0.989	D	0.765	deleterious	None	None	None	None	I
E/Y	0.7994	likely_pathogenic	0.6754	pathogenic	0.177	Stabilizing	0.96	D	0.761	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.