TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6605	20038;20039;20040	chr2:178727765;178727764;178727763	chr2:179592492;179592491;179592490
N2AB	6288	19087;19088;19089	chr2:178727765;178727764;178727763	chr2:179592492;179592491;179592490
N2A	5361	16306;16307;16308	chr2:178727765;178727764;178727763	chr2:179592492;179592491;179592490
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: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-50
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.1796
• 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
I/M	None	None	0.876	D	0.595	0.447	0.498830998431	gnomAD-4.0.0	1.20034E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31252E-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
I/A	0.5952	likely_pathogenic	0.6368	pathogenic	-1.904	Destabilizing	0.821	D	0.552	neutral	None	None	None	None	I
I/C	0.7741	likely_pathogenic	0.7855	pathogenic	-1.055	Destabilizing	0.998	D	0.7	prob.neutral	None	None	None	None	I
I/D	0.9323	likely_pathogenic	0.9331	pathogenic	-1.447	Destabilizing	0.987	D	0.795	deleterious	None	None	None	None	I
I/E	0.8477	likely_pathogenic	0.8476	pathogenic	-1.349	Destabilizing	0.983	D	0.797	deleterious	None	None	None	None	I
I/F	0.2345	likely_benign	0.2365	benign	-1.093	Destabilizing	0.027	N	0.392	neutral	None	None	None	None	I
I/G	0.7951	likely_pathogenic	0.8233	pathogenic	-2.326	Highly Destabilizing	0.957	D	0.778	deleterious	None	None	None	None	I
I/H	0.8248	likely_pathogenic	0.8298	pathogenic	-1.557	Destabilizing	0.999	D	0.812	deleterious	None	None	None	None	I
I/K	0.7691	likely_pathogenic	0.767	pathogenic	-1.408	Destabilizing	0.634	D	0.797	deleterious	D	0.545474321	None	None	I
I/L	0.151	likely_benign	0.159	benign	-0.76	Destabilizing	0.043	N	0.42	neutral	D	0.538758939	None	None	I
I/M	0.1223	likely_benign	0.1178	benign	-0.567	Destabilizing	0.876	D	0.595	neutral	D	0.533446453	None	None	I
I/N	0.5574	ambiguous	0.5612	ambiguous	-1.351	Destabilizing	0.987	D	0.813	deleterious	None	None	None	None	I
I/P	0.8489	likely_pathogenic	0.8827	pathogenic	-1.114	Destabilizing	0.994	D	0.814	deleterious	None	None	None	None	I
I/Q	0.7542	likely_pathogenic	0.7563	pathogenic	-1.389	Destabilizing	0.985	D	0.815	deleterious	None	None	None	None	I
I/R	0.6896	likely_pathogenic	0.6826	pathogenic	-0.937	Destabilizing	0.959	D	0.816	deleterious	D	0.545474321	None	None	I
I/S	0.5734	likely_pathogenic	0.5857	pathogenic	-2.026	Highly Destabilizing	0.918	D	0.739	prob.delet.	None	None	None	None	I
I/T	0.4837	ambiguous	0.4953	ambiguous	-1.8	Destabilizing	0.016	N	0.429	neutral	N	0.518469296	None	None	I
I/V	0.0856	likely_benign	0.0972	benign	-1.114	Destabilizing	None	N	0.203	neutral	N	0.428865236	None	None	I
I/W	0.8534	likely_pathogenic	0.8387	pathogenic	-1.294	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
I/Y	0.618	likely_pathogenic	0.6094	pathogenic	-1.046	Destabilizing	0.646	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.