TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35023	105292;105293;105294	chr2:178531548;178531547;178531546	chr2:179396275;179396274;179396273
N2AB	33382	100369;100370;100371	chr2:178531548;178531547;178531546	chr2:179396275;179396274;179396273
N2A	32455	97588;97589;97590	chr2:178531548;178531547;178531546	chr2:179396275;179396274;179396273
N2B	25958	78097;78098;78099	chr2:178531548;178531547;178531546	chr2:179396275;179396274;179396273
Novex-1	26083	78472;78473;78474	chr2:178531548;178531547;178531546	chr2:179396275;179396274;179396273
Novex-2	26150	78673;78674;78675	chr2:178531548;178531547;178531546	chr2:179396275;179396274;179396273
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-163
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.121
• 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
A/V	None	None	0.885	N	0.565	0.266	0.490282680104	gnomAD-4.0.0	2.05246E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.994E-07	2.31868E-05	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
A/C	0.7242	likely_pathogenic	0.7986	pathogenic	-0.923	Destabilizing	0.252	N	0.483	neutral	None	None	None	None	N
A/D	0.8265	likely_pathogenic	0.8834	pathogenic	-1.077	Destabilizing	0.982	D	0.727	prob.delet.	D	0.525440138	None	None	N
A/E	0.8279	likely_pathogenic	0.8762	pathogenic	-1.185	Destabilizing	0.986	D	0.682	prob.neutral	None	None	None	None	N
A/F	0.7763	likely_pathogenic	0.8442	pathogenic	-1.169	Destabilizing	0.993	D	0.75	deleterious	None	None	None	None	N
A/G	0.4152	ambiguous	0.5294	ambiguous	-0.98	Destabilizing	0.939	D	0.572	neutral	N	0.51657583	None	None	N
A/H	0.9107	likely_pathogenic	0.936	pathogenic	-1.0	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
A/I	0.6381	likely_pathogenic	0.79	pathogenic	-0.577	Destabilizing	0.986	D	0.697	prob.neutral	None	None	None	None	N
A/K	0.946	likely_pathogenic	0.9571	pathogenic	-1.115	Destabilizing	0.986	D	0.671	neutral	None	None	None	None	N
A/L	0.6133	likely_pathogenic	0.7104	pathogenic	-0.577	Destabilizing	0.91	D	0.602	neutral	None	None	None	None	N
A/M	0.5705	likely_pathogenic	0.7067	pathogenic	-0.449	Destabilizing	0.999	D	0.688	prob.neutral	None	None	None	None	N
A/N	0.7281	likely_pathogenic	0.8087	pathogenic	-0.771	Destabilizing	0.986	D	0.741	deleterious	None	None	None	None	N
A/P	0.9929	likely_pathogenic	0.992	pathogenic	-0.621	Destabilizing	0.991	D	0.727	prob.delet.	D	0.528350209	None	None	N
A/Q	0.8232	likely_pathogenic	0.8519	pathogenic	-1.06	Destabilizing	0.993	D	0.728	prob.delet.	None	None	None	None	N
A/R	0.9005	likely_pathogenic	0.9158	pathogenic	-0.604	Destabilizing	0.993	D	0.721	prob.delet.	None	None	None	None	N
A/S	0.18	likely_benign	0.2396	benign	-1.04	Destabilizing	0.885	D	0.565	neutral	D	0.535483774	None	None	N
A/T	0.1929	likely_benign	0.3244	benign	-1.069	Destabilizing	0.17	N	0.305	neutral	N	0.480689284	None	None	N
A/V	0.3232	likely_benign	0.49	ambiguous	-0.621	Destabilizing	0.885	D	0.565	neutral	N	0.516492581	None	None	N
A/W	0.9792	likely_pathogenic	0.9836	pathogenic	-1.351	Destabilizing	0.999	D	0.75	deleterious	None	None	None	None	N
A/Y	0.8929	likely_pathogenic	0.9269	pathogenic	-1.011	Destabilizing	0.998	D	0.748	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.