TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20382	61369;61370;61371	chr2:178590581;178590580;178590579	chr2:179455308;179455307;179455306
N2AB	18741	56446;56447;56448	chr2:178590581;178590580;178590579	chr2:179455308;179455307;179455306
N2A	17814	53665;53666;53667	chr2:178590581;178590580;178590579	chr2:179455308;179455307;179455306
N2B	11317	34174;34175;34176	chr2:178590581;178590580;178590579	chr2:179455308;179455307;179455306
Novex-1	11442	34549;34550;34551	chr2:178590581;178590580;178590579	chr2:179455308;179455307;179455306
Novex-2	11509	34750;34751;34752	chr2:178590581;178590580;178590579	chr2:179455308;179455307;179455306
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: Fn3-36
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.533
• 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/E	None	None	1.0	N	0.389	0.245	0.316788114976	gnomAD-4.0.0	1.5941E-06	None	None	None	None	N	None	0	0	None	0	2.77855E-05	None	0	0	0	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	0.911	likely_pathogenic	0.8549	pathogenic	-0.27	Destabilizing	1.0	D	0.714	prob.delet.	N	0.502453344	None	None	N
D/C	0.9876	likely_pathogenic	0.9819	pathogenic	0.095	Stabilizing	1.0	D	0.662	neutral	None	None	None	None	N
D/E	0.7998	likely_pathogenic	0.7353	pathogenic	-0.331	Destabilizing	1.0	D	0.389	neutral	N	0.475016026	None	None	N
D/F	0.9759	likely_pathogenic	0.967	pathogenic	-0.213	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
D/G	0.8203	likely_pathogenic	0.7306	pathogenic	-0.482	Destabilizing	1.0	D	0.725	prob.delet.	N	0.517961514	None	None	N
D/H	0.9529	likely_pathogenic	0.9216	pathogenic	-0.182	Destabilizing	1.0	D	0.645	neutral	N	0.487564163	None	None	N
D/I	0.9759	likely_pathogenic	0.9614	pathogenic	0.243	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
D/K	0.9808	likely_pathogenic	0.9628	pathogenic	0.339	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
D/L	0.9604	likely_pathogenic	0.9341	pathogenic	0.243	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
D/M	0.9885	likely_pathogenic	0.981	pathogenic	0.431	Stabilizing	1.0	D	0.664	neutral	None	None	None	None	N
D/N	0.6261	likely_pathogenic	0.52	ambiguous	0.032	Stabilizing	1.0	D	0.641	neutral	N	0.519076235	None	None	N
D/P	0.9976	likely_pathogenic	0.9969	pathogenic	0.095	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
D/Q	0.9648	likely_pathogenic	0.9366	pathogenic	0.071	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
D/R	0.978	likely_pathogenic	0.9583	pathogenic	0.443	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
D/S	0.8502	likely_pathogenic	0.765	pathogenic	-0.077	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
D/T	0.9412	likely_pathogenic	0.9046	pathogenic	0.091	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
D/V	0.9248	likely_pathogenic	0.8844	pathogenic	0.095	Stabilizing	1.0	D	0.75	deleterious	N	0.492880081	None	None	N
D/W	0.9939	likely_pathogenic	0.991	pathogenic	-0.083	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	N
D/Y	0.8599	likely_pathogenic	0.8022	pathogenic	0.029	Stabilizing	1.0	D	0.671	neutral	N	0.491678767	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.