TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30310	91153;91154;91155	chr2:178551972;178551971;178551970	chr2:179416699;179416698;179416697
N2AB	28669	86230;86231;86232	chr2:178551972;178551971;178551970	chr2:179416699;179416698;179416697
N2A	27742	83449;83450;83451	chr2:178551972;178551971;178551970	chr2:179416699;179416698;179416697
N2B	21245	63958;63959;63960	chr2:178551972;178551971;178551970	chr2:179416699;179416698;179416697
Novex-1	21370	64333;64334;64335	chr2:178551972;178551971;178551970	chr2:179416699;179416698;179416697
Novex-2	21437	64534;64535;64536	chr2:178551972;178551971;178551970	chr2:179416699;179416698;179416697
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-108
• Domain position: 87
• Structural Position: 120
• Q(SASA): 0.2732
• 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/L	None	None	0.89	N	0.685	0.444	0.677296958874	gnomAD-4.0.0	1.59631E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87219E-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	0.1087	likely_benign	0.1289	benign	-1.622	Destabilizing	0.014	N	0.427	neutral	N	0.464390118	None	None	I
P/C	0.6409	likely_pathogenic	0.7297	pathogenic	-0.968	Destabilizing	0.994	D	0.745	deleterious	None	None	None	None	I
P/D	0.8039	likely_pathogenic	0.8614	pathogenic	-1.713	Destabilizing	0.956	D	0.649	neutral	None	None	None	None	I
P/E	0.6879	likely_pathogenic	0.747	pathogenic	-1.717	Destabilizing	0.86	D	0.613	neutral	None	None	None	None	I
P/F	0.7056	likely_pathogenic	0.788	pathogenic	-1.226	Destabilizing	0.978	D	0.747	deleterious	None	None	None	None	I
P/G	0.405	ambiguous	0.4811	ambiguous	-1.928	Destabilizing	0.754	D	0.554	neutral	None	None	None	None	I
P/H	0.512	ambiguous	0.6081	pathogenic	-1.458	Destabilizing	0.998	D	0.707	prob.neutral	None	None	None	None	I
P/I	0.7011	likely_pathogenic	0.7788	pathogenic	-0.873	Destabilizing	0.956	D	0.734	prob.delet.	None	None	None	None	I
P/K	0.9055	likely_pathogenic	0.9371	pathogenic	-1.496	Destabilizing	0.86	D	0.62	neutral	None	None	None	None	I
P/L	0.4751	ambiguous	0.5927	pathogenic	-0.873	Destabilizing	0.89	D	0.685	prob.neutral	N	0.520664666	None	None	I
P/M	0.6524	likely_pathogenic	0.7437	pathogenic	-0.609	Destabilizing	0.998	D	0.707	prob.neutral	None	None	None	None	I
P/N	0.6509	likely_pathogenic	0.7639	pathogenic	-1.257	Destabilizing	0.956	D	0.675	neutral	None	None	None	None	I
P/Q	0.5696	likely_pathogenic	0.6773	pathogenic	-1.456	Destabilizing	0.97	D	0.699	prob.neutral	D	0.534048887	None	None	I
P/R	0.8361	likely_pathogenic	0.8915	pathogenic	-0.872	Destabilizing	0.97	D	0.693	prob.neutral	D	0.533541908	None	None	I
P/S	0.2015	likely_benign	0.2583	benign	-1.702	Destabilizing	0.153	N	0.358	neutral	N	0.495180578	None	None	I
P/T	0.3042	likely_benign	0.3834	ambiguous	-1.613	Destabilizing	0.698	D	0.557	neutral	D	0.533795398	None	None	I
P/V	0.5189	ambiguous	0.6112	pathogenic	-1.09	Destabilizing	0.915	D	0.64	neutral	None	None	None	None	I
P/W	0.8607	likely_pathogenic	0.9018	pathogenic	-1.427	Destabilizing	0.998	D	0.711	prob.delet.	None	None	None	None	I
P/Y	0.685	likely_pathogenic	0.7577	pathogenic	-1.178	Destabilizing	0.993	D	0.749	deleterious	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.