TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15035	45328;45329;45330	chr2:178621721;178621720;178621719	chr2:179486448;179486447;179486446
N2AB	13394	40405;40406;40407	chr2:178621721;178621720;178621719	chr2:179486448;179486447;179486446
N2A	12467	37624;37625;37626	chr2:178621721;178621720;178621719	chr2:179486448;179486447;179486446
N2B	5970	18133;18134;18135	chr2:178621721;178621720;178621719	chr2:179486448;179486447;179486446
Novex-1	6095	18508;18509;18510	chr2:178621721;178621720;178621719	chr2:179486448;179486447;179486446
Novex-2	6162	18709;18710;18711	chr2:178621721;178621720;178621719	chr2:179486448;179486447;179486446
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-102
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.4819
• 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
K/R	None	None	0.999	N	0.543	0.301	0.444102476654	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
K/A	0.598	likely_pathogenic	0.683	pathogenic	-0.169	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
K/C	0.907	likely_pathogenic	0.9341	pathogenic	-0.178	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
K/D	0.8233	likely_pathogenic	0.8708	pathogenic	0.047	Stabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
K/E	0.3377	likely_benign	0.3672	ambiguous	0.075	Stabilizing	0.999	D	0.587	neutral	N	0.511665423	None	None	N
K/F	0.9614	likely_pathogenic	0.9714	pathogenic	-0.225	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
K/G	0.6251	likely_pathogenic	0.7072	pathogenic	-0.43	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
K/H	0.5258	ambiguous	0.6054	pathogenic	-0.784	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
K/I	0.7892	likely_pathogenic	0.8233	pathogenic	0.456	Stabilizing	1.0	D	0.789	deleterious	D	0.586286171	None	None	N
K/L	0.7482	likely_pathogenic	0.7926	pathogenic	0.456	Stabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
K/M	0.6332	likely_pathogenic	0.6696	pathogenic	0.387	Stabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
K/N	0.6908	likely_pathogenic	0.7427	pathogenic	0.144	Stabilizing	1.0	D	0.7	prob.neutral	D	0.66233487	None	None	N
K/P	0.9686	likely_pathogenic	0.9731	pathogenic	0.277	Stabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
K/Q	0.2373	likely_benign	0.2615	benign	-0.063	Destabilizing	1.0	D	0.675	neutral	N	0.504808992	None	None	N
K/R	0.0894	likely_benign	0.0917	benign	-0.141	Destabilizing	0.999	D	0.543	neutral	N	0.505608003	None	None	N
K/S	0.6452	likely_pathogenic	0.719	pathogenic	-0.426	Destabilizing	0.999	D	0.636	neutral	None	None	None	None	N
K/T	0.4358	ambiguous	0.4933	ambiguous	-0.229	Destabilizing	1.0	D	0.76	deleterious	D	0.54097095	None	None	N
K/V	0.683	likely_pathogenic	0.7409	pathogenic	0.277	Stabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
K/W	0.9245	likely_pathogenic	0.9384	pathogenic	-0.153	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
K/Y	0.8948	likely_pathogenic	0.9164	pathogenic	0.174	Stabilizing	1.0	D	0.749	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.