TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18611	56056;56057;56058	chr2:178601073;178601072;178601071	chr2:179465800;179465799;179465798
N2AB	16970	51133;51134;51135	chr2:178601073;178601072;178601071	chr2:179465800;179465799;179465798
N2A	16043	48352;48353;48354	chr2:178601073;178601072;178601071	chr2:179465800;179465799;179465798
N2B	9546	28861;28862;28863	chr2:178601073;178601072;178601071	chr2:179465800;179465799;179465798
Novex-1	9671	29236;29237;29238	chr2:178601073;178601072;178601071	chr2:179465800;179465799;179465798
Novex-2	9738	29437;29438;29439	chr2:178601073;178601072;178601071	chr2:179465800;179465799;179465798
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-23
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.3471
• 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
V/L	None	None	0.981	N	0.603	0.234	0.381071309025	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-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	0.9223	likely_pathogenic	0.9204	pathogenic	-1.976	Destabilizing	0.998	D	0.685	prob.neutral	N	0.486994732	None	None	I
V/C	0.971	likely_pathogenic	0.977	pathogenic	-1.449	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
V/D	0.995	likely_pathogenic	0.9966	pathogenic	-2.646	Highly Destabilizing	1.0	D	0.901	deleterious	N	0.504338518	None	None	I
V/E	0.9857	likely_pathogenic	0.9882	pathogenic	-2.524	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	I
V/F	0.9486	likely_pathogenic	0.9553	pathogenic	-1.361	Destabilizing	0.999	D	0.879	deleterious	N	0.48792933	None	None	I
V/G	0.9655	likely_pathogenic	0.9677	pathogenic	-2.421	Highly Destabilizing	1.0	D	0.885	deleterious	N	0.51746925	None	None	I
V/H	0.996	likely_pathogenic	0.997	pathogenic	-2.192	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
V/I	0.1016	likely_benign	0.0982	benign	-0.777	Destabilizing	0.767	D	0.34	neutral	N	0.393608151	None	None	I
V/K	0.9908	likely_pathogenic	0.9925	pathogenic	-1.722	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	I
V/L	0.7872	likely_pathogenic	0.8022	pathogenic	-0.777	Destabilizing	0.981	D	0.603	neutral	N	0.49121763	None	None	I
V/M	0.8168	likely_pathogenic	0.8335	pathogenic	-0.631	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	I
V/N	0.9593	likely_pathogenic	0.9749	pathogenic	-1.819	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	I
V/P	0.923	likely_pathogenic	0.9302	pathogenic	-1.147	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	I
V/Q	0.9869	likely_pathogenic	0.9881	pathogenic	-1.826	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	I
V/R	0.9826	likely_pathogenic	0.9859	pathogenic	-1.339	Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	I
V/S	0.9586	likely_pathogenic	0.965	pathogenic	-2.341	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	I
V/T	0.899	likely_pathogenic	0.9115	pathogenic	-2.102	Highly Destabilizing	0.998	D	0.839	deleterious	None	None	None	None	I
V/W	0.9988	likely_pathogenic	0.9991	pathogenic	-1.847	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	I
V/Y	0.993	likely_pathogenic	0.995	pathogenic	-1.493	Destabilizing	1.0	D	0.878	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.