TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9647	29164;29165;29166	chr2:178707628;178707627;178707626	chr2:179572355;179572354;179572353
N2AB	9330	28213;28214;28215	chr2:178707628;178707627;178707626	chr2:179572355;179572354;179572353
N2A	8403	25432;25433;25434	chr2:178707628;178707627;178707626	chr2:179572355;179572354;179572353
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-82
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0759
• 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
L/M	None	-0.916	1.0	None	0.78	0.569	0.709279802104	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
L/M	None	-0.916	1.0	None	0.78	0.569	0.709279802104	gnomAD-4.0.0	1.59119E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85788E-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
L/A	0.882	likely_pathogenic	0.8387	pathogenic	-2.389	Highly Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
L/C	0.8765	likely_pathogenic	0.8529	pathogenic	-1.704	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/D	0.9995	likely_pathogenic	0.9993	pathogenic	-3.217	Highly Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/E	0.9945	likely_pathogenic	0.9934	pathogenic	-2.894	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
L/F	0.3886	ambiguous	0.3338	benign	-1.485	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
L/G	0.9795	likely_pathogenic	0.9701	pathogenic	-3.005	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
L/H	0.9848	likely_pathogenic	0.9782	pathogenic	-2.834	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
L/I	0.2749	likely_benign	0.2444	benign	-0.55	Destabilizing	0.999	D	0.672	neutral	None	None	None	None	N
L/K	0.9906	likely_pathogenic	0.9889	pathogenic	-1.86	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
L/M	0.2145	likely_benign	0.1963	benign	-0.712	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
L/N	0.9966	likely_pathogenic	0.9956	pathogenic	-2.587	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/P	0.996	likely_pathogenic	0.9948	pathogenic	-1.152	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/Q	0.9692	likely_pathogenic	0.9606	pathogenic	-2.224	Highly Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
L/R	0.9757	likely_pathogenic	0.9688	pathogenic	-1.986	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/S	0.9867	likely_pathogenic	0.978	pathogenic	-3.143	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
L/T	0.9555	likely_pathogenic	0.9313	pathogenic	-2.645	Highly Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
L/V	0.2975	likely_benign	0.2573	benign	-1.152	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
L/W	0.9021	likely_pathogenic	0.8546	pathogenic	-1.948	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
L/Y	0.9377	likely_pathogenic	0.9259	pathogenic	-1.638	Destabilizing	1.0	D	0.85	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.