TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20982	63169;63170;63171	chr2:178588781;178588780;178588779	chr2:179453508;179453507;179453506
N2AB	19341	58246;58247;58248	chr2:178588781;178588780;178588779	chr2:179453508;179453507;179453506
N2A	18414	55465;55466;55467	chr2:178588781;178588780;178588779	chr2:179453508;179453507;179453506
N2B	11917	35974;35975;35976	chr2:178588781;178588780;178588779	chr2:179453508;179453507;179453506
Novex-1	12042	36349;36350;36351	chr2:178588781;178588780;178588779	chr2:179453508;179453507;179453506
Novex-2	12109	36550;36551;36552	chr2:178588781;178588780;178588779	chr2:179453508;179453507;179453506
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-40
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.1222
• 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/L	None	None	0.997	N	0.691	0.352	0.461495907335	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
V/A	0.8185	likely_pathogenic	0.7682	pathogenic	-2.301	Highly Destabilizing	0.999	D	0.696	prob.neutral	N	0.483160071	None	None	N
V/C	0.9703	likely_pathogenic	0.9619	pathogenic	-1.872	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
V/D	0.9996	likely_pathogenic	0.9993	pathogenic	-3.406	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
V/E	0.998	likely_pathogenic	0.9972	pathogenic	-3.093	Highly Destabilizing	1.0	D	0.798	deleterious	N	0.518242946	None	None	N
V/F	0.9623	likely_pathogenic	0.9456	pathogenic	-1.308	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
V/G	0.9775	likely_pathogenic	0.9641	pathogenic	-2.917	Highly Destabilizing	1.0	D	0.814	deleterious	N	0.495530335	None	None	N
V/H	0.9996	likely_pathogenic	0.9993	pathogenic	-2.889	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
V/I	0.1024	likely_benign	0.1007	benign	-0.518	Destabilizing	0.998	D	0.559	neutral	None	None	None	None	N
V/K	0.9986	likely_pathogenic	0.9979	pathogenic	-1.985	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
V/L	0.449	ambiguous	0.3635	ambiguous	-0.518	Destabilizing	0.997	D	0.691	prob.neutral	N	0.39119699	None	None	N
V/M	0.7492	likely_pathogenic	0.674	pathogenic	-0.765	Destabilizing	1.0	D	0.7	prob.neutral	N	0.481185062	None	None	N
V/N	0.9982	likely_pathogenic	0.9973	pathogenic	-2.643	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
V/P	0.9982	likely_pathogenic	0.9966	pathogenic	-1.093	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
V/Q	0.998	likely_pathogenic	0.997	pathogenic	-2.298	Highly Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
V/R	0.997	likely_pathogenic	0.9954	pathogenic	-2.049	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
V/S	0.9875	likely_pathogenic	0.9809	pathogenic	-3.167	Highly Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
V/T	0.923	likely_pathogenic	0.899	pathogenic	-2.693	Highly Destabilizing	0.999	D	0.676	prob.neutral	None	None	None	None	N
V/W	0.9997	likely_pathogenic	0.9995	pathogenic	-1.962	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
V/Y	0.9981	likely_pathogenic	0.9971	pathogenic	-1.59	Destabilizing	1.0	D	0.7	prob.neutral	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.