TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29065	87418;87419;87420	chr2:178558161;178558160;178558159	chr2:179422888;179422887;179422886
N2AB	27424	82495;82496;82497	chr2:178558161;178558160;178558159	chr2:179422888;179422887;179422886
N2A	26497	79714;79715;79716	chr2:178558161;178558160;178558159	chr2:179422888;179422887;179422886
N2B	20000	60223;60224;60225	chr2:178558161;178558160;178558159	chr2:179422888;179422887;179422886
Novex-1	20125	60598;60599;60600	chr2:178558161;178558160;178558159	chr2:179422888;179422887;179422886
Novex-2	20192	60799;60800;60801	chr2:178558161;178558160;178558159	chr2:179422888;179422887;179422886
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-145
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.2296
• 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
D/N	None	None	0.896	N	0.442	0.291	0.357929162469	gnomAD-4.0.0	1.36847E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79888E-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
D/A	0.1942	likely_benign	0.1497	benign	-0.435	Destabilizing	0.896	D	0.592	neutral	N	0.494962516	None	None	N
D/C	0.6599	likely_pathogenic	0.5338	ambiguous	-0.227	Destabilizing	0.999	D	0.762	deleterious	None	None	None	None	N
D/E	0.1548	likely_benign	0.1156	benign	-0.743	Destabilizing	0.004	N	0.193	neutral	N	0.397875899	None	None	N
D/F	0.6759	likely_pathogenic	0.571	pathogenic	0.011	Stabilizing	0.996	D	0.738	prob.delet.	None	None	None	None	N
D/G	0.269	likely_benign	0.2132	benign	-0.789	Destabilizing	0.896	D	0.519	neutral	N	0.514761785	None	None	N
D/H	0.3392	likely_benign	0.2569	benign	-0.246	Destabilizing	0.984	D	0.645	neutral	N	0.477320905	None	None	N
D/I	0.3277	likely_benign	0.2509	benign	0.495	Stabilizing	0.988	D	0.713	prob.delet.	None	None	None	None	N
D/K	0.5066	ambiguous	0.3977	ambiguous	-0.334	Destabilizing	0.851	D	0.522	neutral	None	None	None	None	N
D/L	0.4416	ambiguous	0.3497	ambiguous	0.495	Stabilizing	0.976	D	0.661	neutral	None	None	None	None	N
D/M	0.5853	likely_pathogenic	0.481	ambiguous	0.846	Stabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
D/N	0.113	likely_benign	0.0932	benign	-0.864	Destabilizing	0.896	D	0.442	neutral	N	0.446053848	None	None	N
D/P	0.8217	likely_pathogenic	0.7136	pathogenic	0.211	Stabilizing	0.988	D	0.588	neutral	None	None	None	None	N
D/Q	0.3614	ambiguous	0.2779	benign	-0.696	Destabilizing	0.851	D	0.458	neutral	None	None	None	None	N
D/R	0.5474	ambiguous	0.4368	ambiguous	-0.125	Destabilizing	0.976	D	0.639	neutral	None	None	None	None	N
D/S	0.1555	likely_benign	0.1215	benign	-1.054	Destabilizing	0.919	D	0.473	neutral	None	None	None	None	N
D/T	0.2289	likely_benign	0.1788	benign	-0.761	Destabilizing	0.919	D	0.519	neutral	None	None	None	None	N
D/V	0.1938	likely_benign	0.1481	benign	0.211	Stabilizing	0.984	D	0.667	neutral	N	0.47139501	None	None	N
D/W	0.9361	likely_pathogenic	0.8988	pathogenic	0.187	Stabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
D/Y	0.3255	likely_benign	0.2566	benign	0.247	Stabilizing	0.995	D	0.735	prob.delet.	N	0.514935143	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.