TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28405	85438;85439;85440	chr2:178560919;178560918;178560917	chr2:179425646;179425645;179425644
N2AB	26764	80515;80516;80517	chr2:178560919;178560918;178560917	chr2:179425646;179425645;179425644
N2A	25837	77734;77735;77736	chr2:178560919;178560918;178560917	chr2:179425646;179425645;179425644
N2B	19340	58243;58244;58245	chr2:178560919;178560918;178560917	chr2:179425646;179425645;179425644
Novex-1	19465	58618;58619;58620	chr2:178560919;178560918;178560917	chr2:179425646;179425645;179425644
Novex-2	19532	58819;58820;58821	chr2:178560919;178560918;178560917	chr2:179425646;179425645;179425644
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: Ig-143
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.1864
• 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/V	None	None	0.988	N	0.785	0.471	0.693353280975	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	0.2131	likely_benign	0.2087	benign	-0.979	Destabilizing	0.958	D	0.543	neutral	N	0.494517874	None	None	N
E/C	0.8873	likely_pathogenic	0.8853	pathogenic	-0.461	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/D	0.1887	likely_benign	0.1874	benign	-1.134	Destabilizing	0.958	D	0.413	neutral	N	0.489428993	None	None	N
E/F	0.841	likely_pathogenic	0.8269	pathogenic	-0.611	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
E/G	0.2648	likely_benign	0.2402	benign	-1.332	Destabilizing	0.988	D	0.687	prob.neutral	N	0.504432602	None	None	N
E/H	0.498	ambiguous	0.4798	ambiguous	-0.941	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
E/I	0.4435	ambiguous	0.4412	ambiguous	-0.017	Destabilizing	0.995	D	0.843	deleterious	None	None	None	None	N
E/K	0.1693	likely_benign	0.153	benign	-0.527	Destabilizing	0.919	D	0.443	neutral	N	0.478126194	None	None	N
E/L	0.5629	ambiguous	0.5478	ambiguous	-0.017	Destabilizing	0.991	D	0.799	deleterious	None	None	None	None	N
E/M	0.5244	ambiguous	0.5141	ambiguous	0.494	Stabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
E/N	0.3039	likely_benign	0.3068	benign	-0.966	Destabilizing	0.991	D	0.68	prob.neutral	None	None	None	None	N
E/P	0.9675	likely_pathogenic	0.9635	pathogenic	-0.317	Destabilizing	0.995	D	0.813	deleterious	None	None	None	None	N
E/Q	0.1509	likely_benign	0.1479	benign	-0.851	Destabilizing	0.414	N	0.253	neutral	N	0.495501234	None	None	N
E/R	0.3034	likely_benign	0.2773	benign	-0.387	Destabilizing	0.982	D	0.671	neutral	None	None	None	None	N
E/S	0.2402	likely_benign	0.2461	benign	-1.302	Destabilizing	0.968	D	0.534	neutral	None	None	None	None	N
E/T	0.2423	likely_benign	0.2481	benign	-0.997	Destabilizing	0.991	D	0.719	prob.delet.	None	None	None	None	N
E/V	0.2599	likely_benign	0.2574	benign	-0.317	Destabilizing	0.988	D	0.785	deleterious	N	0.519167527	None	None	N
E/W	0.9447	likely_pathogenic	0.9324	pathogenic	-0.383	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/Y	0.7363	likely_pathogenic	0.7073	pathogenic	-0.344	Destabilizing	0.998	D	0.833	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.