TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32642	98149;98150;98151	chr2:178540242;178540241;178540240	chr2:179404969;179404968;179404967
N2AB	31001	93226;93227;93228	chr2:178540242;178540241;178540240	chr2:179404969;179404968;179404967
N2A	30074	90445;90446;90447	chr2:178540242;178540241;178540240	chr2:179404969;179404968;179404967
N2B	23577	70954;70955;70956	chr2:178540242;178540241;178540240	chr2:179404969;179404968;179404967
Novex-1	23702	71329;71330;71331	chr2:178540242;178540241;178540240	chr2:179404969;179404968;179404967
Novex-2	23769	71530;71531;71532	chr2:178540242;178540241;178540240	chr2:179404969;179404968;179404967
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: Fn3-126
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.4365
• 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/A	rs1575367028	None	0.999	N	0.591	0.354	0.59360226722	gnomAD-4.0.0	1.59116E-06	None	None	None	None	N	None	0	0	None	0	2.77254E-05	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	0.0919	likely_benign	0.0938	benign	-1.336	Destabilizing	0.999	D	0.591	neutral	N	0.443637113	None	None	N
V/C	0.7338	likely_pathogenic	0.7468	pathogenic	-0.809	Destabilizing	1.0	D	0.645	neutral	None	None	None	None	N
V/D	0.3063	likely_benign	0.3974	ambiguous	-1.254	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
V/E	0.2569	likely_benign	0.3065	benign	-1.304	Destabilizing	1.0	D	0.695	prob.neutral	N	0.44948565	None	None	N
V/F	0.2851	likely_benign	0.3518	ambiguous	-1.141	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
V/G	0.1812	likely_benign	0.2081	benign	-1.592	Destabilizing	1.0	D	0.701	prob.neutral	N	0.488390755	None	None	N
V/H	0.6367	likely_pathogenic	0.6891	pathogenic	-1.088	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
V/I	0.0866	likely_benign	0.0888	benign	-0.754	Destabilizing	0.997	D	0.489	neutral	N	0.473498661	None	None	N
V/K	0.3235	likely_benign	0.3723	ambiguous	-1.187	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
V/L	0.2318	likely_benign	0.2475	benign	-0.754	Destabilizing	0.997	D	0.575	neutral	N	0.475498816	None	None	N
V/M	0.1583	likely_benign	0.1815	benign	-0.529	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
V/N	0.2649	likely_benign	0.2904	benign	-0.879	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
V/P	0.2533	likely_benign	0.2763	benign	-0.913	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
V/Q	0.3478	ambiguous	0.375	ambiguous	-1.128	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
V/R	0.3412	ambiguous	0.4026	ambiguous	-0.548	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
V/S	0.165	likely_benign	0.1728	benign	-1.306	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
V/T	0.1102	likely_benign	0.1073	benign	-1.262	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
V/W	0.8308	likely_pathogenic	0.8903	pathogenic	-1.267	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
V/Y	0.6357	likely_pathogenic	0.6996	pathogenic	-1.018	Destabilizing	1.0	D	0.69	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.