TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19870	59833;59834;59835	chr2:178592397;178592396;178592395	chr2:179457124;179457123;179457122
N2AB	18229	54910;54911;54912	chr2:178592397;178592396;178592395	chr2:179457124;179457123;179457122
N2A	17302	52129;52130;52131	chr2:178592397;178592396;178592395	chr2:179457124;179457123;179457122
N2B	10805	32638;32639;32640	chr2:178592397;178592396;178592395	chr2:179457124;179457123;179457122
Novex-1	10930	33013;33014;33015	chr2:178592397;178592396;178592395	chr2:179457124;179457123;179457122
Novex-2	10997	33214;33215;33216	chr2:178592397;178592396;178592395	chr2:179457124;179457123;179457122
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-119
• Domain position: 81
• Structural Position: 172
• Q(SASA): 0.0994
• 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
V/G	None	None	0.994	N	0.81	0.523	0.83695693211	gnomAD-4.0.0	1.59326E-06	None	None	None	None	N	None	5.67795E-05	0	None	0	0	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
V/A	0.7175	likely_pathogenic	0.67	pathogenic	-2.04	Highly Destabilizing	0.91	D	0.585	neutral	N	0.492690215	None	None	N
V/C	0.8439	likely_pathogenic	0.792	pathogenic	-1.748	Destabilizing	0.092	N	0.419	neutral	None	None	None	None	N
V/D	0.9916	likely_pathogenic	0.9928	pathogenic	-2.572	Highly Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
V/E	0.9791	likely_pathogenic	0.9838	pathogenic	-2.371	Highly Destabilizing	0.998	D	0.791	deleterious	N	0.520387718	None	None	N
V/F	0.583	likely_pathogenic	0.5681	pathogenic	-1.238	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
V/G	0.8159	likely_pathogenic	0.8248	pathogenic	-2.567	Highly Destabilizing	0.994	D	0.81	deleterious	N	0.497675107	None	None	N
V/H	0.9867	likely_pathogenic	0.9882	pathogenic	-2.32	Highly Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
V/I	0.1173	likely_benign	0.1053	benign	-0.583	Destabilizing	0.954	D	0.639	neutral	N	0.49940833	None	None	N
V/K	0.9746	likely_pathogenic	0.982	pathogenic	-1.688	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
V/L	0.5893	likely_pathogenic	0.5479	ambiguous	-0.583	Destabilizing	0.91	D	0.577	neutral	N	0.512566842	None	None	N
V/M	0.5171	ambiguous	0.4601	ambiguous	-0.72	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	N
V/N	0.9609	likely_pathogenic	0.961	pathogenic	-1.977	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
V/P	0.9913	likely_pathogenic	0.9935	pathogenic	-1.04	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
V/Q	0.9578	likely_pathogenic	0.9683	pathogenic	-1.843	Destabilizing	0.999	D	0.777	deleterious	None	None	None	None	N
V/R	0.9536	likely_pathogenic	0.9695	pathogenic	-1.513	Destabilizing	0.999	D	0.822	deleterious	None	None	None	None	N
V/S	0.8793	likely_pathogenic	0.867	pathogenic	-2.612	Highly Destabilizing	0.985	D	0.785	deleterious	None	None	None	None	N
V/T	0.6901	likely_pathogenic	0.629	pathogenic	-2.267	Highly Destabilizing	0.985	D	0.665	neutral	None	None	None	None	N
V/W	0.9886	likely_pathogenic	0.9896	pathogenic	-1.733	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
V/Y	0.9558	likely_pathogenic	0.9582	pathogenic	-1.354	Destabilizing	0.999	D	0.784	deleterious	None	None	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.