TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19977	60154;60155;60156	chr2:178591890;178591889;178591888	chr2:179456617;179456616;179456615
N2AB	18336	55231;55232;55233	chr2:178591890;178591889;178591888	chr2:179456617;179456616;179456615
N2A	17409	52450;52451;52452	chr2:178591890;178591889;178591888	chr2:179456617;179456616;179456615
N2B	10912	32959;32960;32961	chr2:178591890;178591889;178591888	chr2:179456617;179456616;179456615
Novex-1	11037	33334;33335;33336	chr2:178591890;178591889;178591888	chr2:179456617;179456616;179456615
Novex-2	11104	33535;33536;33537	chr2:178591890;178591889;178591888	chr2:179456617;179456616;179456615
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: Fn3-33
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.4352
• 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/T	rs768561791	-0.232	1.0	N	0.798	0.316	0.371344866733	gnomAD-2.1.1	8.31E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.82E-05	0
P/T	rs768561791	-0.232	1.0	N	0.798	0.316	0.371344866733	gnomAD-4.0.0	1.60914E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87322E-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	0.1089	likely_benign	0.1122	benign	-0.489	Destabilizing	0.999	D	0.765	deleterious	N	0.510144533	None	None	I
P/C	0.5739	likely_pathogenic	0.6498	pathogenic	-0.622	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
P/D	0.8549	likely_pathogenic	0.8824	pathogenic	-0.117	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	I
P/E	0.4754	ambiguous	0.5083	ambiguous	-0.238	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
P/F	0.6885	likely_pathogenic	0.7402	pathogenic	-0.795	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
P/G	0.6745	likely_pathogenic	0.7112	pathogenic	-0.606	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	I
P/H	0.3758	ambiguous	0.4241	ambiguous	-0.202	Destabilizing	1.0	D	0.835	deleterious	N	0.488722117	None	None	I
P/I	0.2517	likely_benign	0.2917	benign	-0.335	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
P/K	0.3877	ambiguous	0.4298	ambiguous	-0.257	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
P/L	0.1821	likely_benign	0.2052	benign	-0.335	Destabilizing	1.0	D	0.805	deleterious	N	0.512742121	None	None	I
P/M	0.3971	ambiguous	0.433	ambiguous	-0.273	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
P/N	0.6851	likely_pathogenic	0.7278	pathogenic	-0.021	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
P/Q	0.2465	likely_benign	0.2649	benign	-0.296	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
P/R	0.2783	likely_benign	0.3123	benign	0.235	Stabilizing	1.0	D	0.833	deleterious	N	0.50910717	None	None	I
P/S	0.264	likely_benign	0.2836	benign	-0.421	Destabilizing	1.0	D	0.818	deleterious	N	0.474225486	None	None	I
P/T	0.163	likely_benign	0.1814	benign	-0.442	Destabilizing	1.0	D	0.798	deleterious	N	0.51405163	None	None	I
P/V	0.1795	likely_benign	0.199	benign	-0.352	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
P/W	0.8844	likely_pathogenic	0.9134	pathogenic	-0.84	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
P/Y	0.6747	likely_pathogenic	0.7368	pathogenic	-0.518	Destabilizing	1.0	D	0.838	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.