TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26574	79945;79946;79947	chr2:178566412;178566411;178566410	chr2:179431139;179431138;179431137
N2AB	24933	75022;75023;75024	chr2:178566412;178566411;178566410	chr2:179431139;179431138;179431137
N2A	24006	72241;72242;72243	chr2:178566412;178566411;178566410	chr2:179431139;179431138;179431137
N2B	17509	52750;52751;52752	chr2:178566412;178566411;178566410	chr2:179431139;179431138;179431137
Novex-1	17634	53125;53126;53127	chr2:178566412;178566411;178566410	chr2:179431139;179431138;179431137
Novex-2	17701	53326;53327;53328	chr2:178566412;178566411;178566410	chr2:179431139;179431138;179431137
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: Fn3-81
• Domain position: 88
• Structural Position: 120
• Q(SASA): 0.2405
• Predicted PPI site: I

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/D	None	None	0.497	N	0.63	0.319	0.410469974859	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.3862	ambiguous	0.4278	ambiguous	-0.973	Destabilizing	0.968	D	0.537	neutral	None	None	None	None	I
A/D	0.2556	likely_benign	0.3105	benign	-1.406	Destabilizing	0.497	N	0.63	neutral	N	0.483779077	None	None	I
A/E	0.2408	likely_benign	0.2872	benign	-1.523	Destabilizing	0.272	N	0.573	neutral	None	None	None	None	I
A/F	0.2665	likely_benign	0.2801	benign	-1.352	Destabilizing	0.89	D	0.725	prob.delet.	None	None	None	None	I
A/G	0.1328	likely_benign	0.1435	benign	-1.084	Destabilizing	0.22	N	0.539	neutral	N	0.468521623	None	None	I
A/H	0.398	ambiguous	0.4329	ambiguous	-1.08	Destabilizing	0.968	D	0.715	prob.delet.	None	None	None	None	I
A/I	0.268	likely_benign	0.2983	benign	-0.755	Destabilizing	0.726	D	0.635	neutral	None	None	None	None	I
A/K	0.5027	ambiguous	0.5745	pathogenic	-1.172	Destabilizing	0.272	N	0.57	neutral	None	None	None	None	I
A/L	0.2273	likely_benign	0.2513	benign	-0.755	Destabilizing	0.272	N	0.561	neutral	None	None	None	None	I
A/M	0.2325	likely_benign	0.2612	benign	-0.533	Destabilizing	0.968	D	0.649	neutral	None	None	None	None	I
A/N	0.2165	likely_benign	0.2674	benign	-0.841	Destabilizing	0.726	D	0.694	prob.neutral	None	None	None	None	I
A/P	0.0805	likely_benign	0.0794	benign	-0.784	Destabilizing	None	N	0.393	neutral	N	0.298897331	None	None	I
A/Q	0.3445	ambiguous	0.3818	ambiguous	-1.182	Destabilizing	0.726	D	0.644	neutral	None	None	None	None	I
A/R	0.5059	ambiguous	0.559	ambiguous	-0.622	Destabilizing	0.726	D	0.635	neutral	None	None	None	None	I
A/S	0.0913	likely_benign	0.0998	benign	-1.064	Destabilizing	0.22	N	0.555	neutral	N	0.46092086	None	None	I
A/T	0.1129	likely_benign	0.1283	benign	-1.115	Destabilizing	0.22	N	0.508	neutral	N	0.472041931	None	None	I
A/V	0.1492	likely_benign	0.1622	benign	-0.784	Destabilizing	0.22	N	0.511	neutral	N	0.452903729	None	None	I
A/W	0.6515	likely_pathogenic	0.6871	pathogenic	-1.496	Destabilizing	0.968	D	0.752	deleterious	None	None	None	None	I
A/Y	0.3374	likely_benign	0.3626	ambiguous	-1.179	Destabilizing	0.89	D	0.725	prob.delet.	None	None	None	None	I

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.