TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6040	18343;18344;18345	chr2:178730282;178730281;178730280	chr2:179595009;179595008;179595007
N2AB	5723	17392;17393;17394	chr2:178730282;178730281;178730280	chr2:179595009;179595008;179595007
N2A	4796	14611;14612;14613	chr2:178730282;178730281;178730280	chr2:179595009;179595008;179595007
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: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-44
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.7724
• 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
P/S	None	None	1.0	N	0.681	0.469	0.516050471323	gnomAD-4.0.0	6.84735E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	1.65815E-05
P/T	None	None	1.0	D	0.672	0.471	0.635285018509	gnomAD-4.0.0	1.36947E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79968E-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
P/A	0.2291	likely_benign	0.203	benign	-0.202	Destabilizing	1.0	D	0.66	neutral	N	0.486008725	None	None	I
P/C	0.8783	likely_pathogenic	0.8325	pathogenic	-0.316	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	I
P/D	0.7053	likely_pathogenic	0.6667	pathogenic	-0.411	Destabilizing	1.0	D	0.656	neutral	None	None	None	None	I
P/E	0.5847	likely_pathogenic	0.5207	ambiguous	-0.558	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
P/F	0.8397	likely_pathogenic	0.8253	pathogenic	-0.729	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	I
P/G	0.5689	likely_pathogenic	0.5357	ambiguous	-0.274	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	I
P/H	0.5369	ambiguous	0.4842	ambiguous	-0.048	Destabilizing	1.0	D	0.636	neutral	D	0.52991669	None	None	I
P/I	0.6968	likely_pathogenic	0.6517	pathogenic	-0.173	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	I
P/K	0.6249	likely_pathogenic	0.5521	ambiguous	-0.184	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	I
P/L	0.3865	ambiguous	0.3442	ambiguous	-0.173	Destabilizing	1.0	D	0.682	prob.neutral	N	0.501176919	None	None	I
P/M	0.6941	likely_pathogenic	0.6525	pathogenic	-0.195	Destabilizing	1.0	D	0.64	neutral	None	None	None	None	I
P/N	0.5733	likely_pathogenic	0.5369	ambiguous	0.207	Stabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
P/Q	0.4384	ambiguous	0.3828	ambiguous	-0.097	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	I
P/R	0.4907	ambiguous	0.4245	ambiguous	0.302	Stabilizing	1.0	D	0.666	neutral	N	0.489820613	None	None	I
P/S	0.3312	likely_benign	0.2988	benign	-0.037	Destabilizing	1.0	D	0.681	prob.neutral	N	0.494162253	None	None	I
P/T	0.3096	likely_benign	0.2745	benign	-0.099	Destabilizing	1.0	D	0.672	neutral	D	0.527938939	None	None	I
P/V	0.5238	ambiguous	0.4847	ambiguous	-0.151	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	I
P/W	0.9372	likely_pathogenic	0.9262	pathogenic	-0.814	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	I
P/Y	0.8173	likely_pathogenic	0.7935	pathogenic	-0.483	Destabilizing	1.0	D	0.635	neutral	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.