TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30777	92554;92555;92556	chr2:178549297;178549296;178549295	chr2:179414024;179414023;179414022
N2AB	29136	87631;87632;87633	chr2:178549297;178549296;178549295	chr2:179414024;179414023;179414022
N2A	28209	84850;84851;84852	chr2:178549297;178549296;178549295	chr2:179414024;179414023;179414022
N2B	21712	65359;65360;65361	chr2:178549297;178549296;178549295	chr2:179414024;179414023;179414022
Novex-1	21837	65734;65735;65736	chr2:178549297;178549296;178549295	chr2:179414024;179414023;179414022
Novex-2	21904	65935;65936;65937	chr2:178549297;178549296;178549295	chr2:179414024;179414023;179414022
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: Fn3-112
• Domain position: 59
• Structural Position: 88
• Q(SASA): 0.3715
• 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
E/A	None	None	0.928	N	0.687	0.397	0.338834610459	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
E/K	None	None	0.928	N	0.559	0.306	0.306695030598	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
E/A	0.5336	ambiguous	0.536	ambiguous	-0.104	Destabilizing	0.928	D	0.687	prob.neutral	N	0.484446373	None	None	N
E/C	0.9747	likely_pathogenic	0.976	pathogenic	-0.227	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
E/D	0.1813	likely_benign	0.175	benign	-0.366	Destabilizing	0.039	N	0.198	neutral	N	0.407969889	None	None	N
E/F	0.9703	likely_pathogenic	0.9721	pathogenic	0.292	Stabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
E/G	0.4401	ambiguous	0.4468	ambiguous	-0.327	Destabilizing	0.978	D	0.741	deleterious	N	0.505555151	None	None	N
E/H	0.8677	likely_pathogenic	0.8779	pathogenic	0.747	Stabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
E/I	0.9166	likely_pathogenic	0.9173	pathogenic	0.458	Stabilizing	0.992	D	0.793	deleterious	None	None	None	None	N
E/K	0.6616	likely_pathogenic	0.6459	pathogenic	0.507	Stabilizing	0.928	D	0.559	neutral	N	0.515673357	None	None	N
E/L	0.8995	likely_pathogenic	0.8941	pathogenic	0.458	Stabilizing	0.992	D	0.775	deleterious	None	None	None	None	N
E/M	0.8974	likely_pathogenic	0.8994	pathogenic	0.252	Stabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
E/N	0.6243	likely_pathogenic	0.6367	pathogenic	-0.146	Destabilizing	0.968	D	0.703	prob.neutral	None	None	None	None	N
E/P	0.9621	likely_pathogenic	0.9653	pathogenic	0.291	Stabilizing	0.992	D	0.777	deleterious	None	None	None	None	N
E/Q	0.445	ambiguous	0.4441	ambiguous	-0.039	Destabilizing	0.989	D	0.649	neutral	N	0.504707002	None	None	N
E/R	0.7707	likely_pathogenic	0.7732	pathogenic	0.836	Stabilizing	0.992	D	0.705	prob.neutral	None	None	None	None	N
E/S	0.529	ambiguous	0.552	ambiguous	-0.248	Destabilizing	0.944	D	0.609	neutral	None	None	None	None	N
E/T	0.6955	likely_pathogenic	0.6983	pathogenic	-0.039	Destabilizing	0.983	D	0.767	deleterious	None	None	None	None	N
E/V	0.761	likely_pathogenic	0.7625	pathogenic	0.291	Stabilizing	0.989	D	0.762	deleterious	N	0.498666464	None	None	N
E/W	0.9907	likely_pathogenic	0.9909	pathogenic	0.483	Stabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
E/Y	0.9389	likely_pathogenic	0.9399	pathogenic	0.562	Stabilizing	0.999	D	0.773	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.