TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15421	46486;46487;46488	chr2:178620260;178620259;178620258	chr2:179484987;179484986;179484985
N2AB	13780	41563;41564;41565	chr2:178620260;178620259;178620258	chr2:179484987;179484986;179484985
N2A	12853	38782;38783;38784	chr2:178620260;178620259;178620258	chr2:179484987;179484986;179484985
N2B	6356	19291;19292;19293	chr2:178620260;178620259;178620258	chr2:179484987;179484986;179484985
Novex-1	6481	19666;19667;19668	chr2:178620260;178620259;178620258	chr2:179484987;179484986;179484985
Novex-2	6548	19867;19868;19869	chr2:178620260;178620259;178620258	chr2:179484987;179484986;179484985
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-106
• Domain position: 31
• Structural Position: 46
• Q(SASA): 0.2726
• 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/I	rs1182471718	-0.636	0.248	N	0.329	0.227	0.636377056752	gnomAD-2.1.1	5.26E-06	None	None	None	None	N	None	0	4.18E-05	None	0	0	None	0	None	0	0	0
V/I	rs1182471718	-0.636	0.248	N	0.329	0.227	0.636377056752	gnomAD-4.0.0	1.79914E-06	None	None	None	None	N	None	0	3.12656E-05	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	0.4652	ambiguous	0.6169	pathogenic	-1.555	Destabilizing	0.122	N	0.321	neutral	D	0.614253997	None	None	N
V/C	0.8909	likely_pathogenic	0.9397	pathogenic	-0.685	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
V/D	0.9705	likely_pathogenic	0.9821	pathogenic	-1.621	Destabilizing	0.996	D	0.849	deleterious	None	None	None	None	N
V/E	0.9373	likely_pathogenic	0.9616	pathogenic	-1.581	Destabilizing	0.994	D	0.833	deleterious	D	0.746610291	None	None	N
V/F	0.7117	likely_pathogenic	0.8091	pathogenic	-1.171	Destabilizing	0.996	D	0.757	deleterious	None	None	None	None	N
V/G	0.7148	likely_pathogenic	0.8035	pathogenic	-1.892	Destabilizing	0.961	D	0.812	deleterious	D	0.569956707	None	None	N
V/H	0.9816	likely_pathogenic	0.9899	pathogenic	-1.492	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
V/I	0.1076	likely_benign	0.1271	benign	-0.697	Destabilizing	0.248	N	0.329	neutral	N	0.50686041	None	None	N
V/K	0.9516	likely_pathogenic	0.9694	pathogenic	-1.227	Destabilizing	0.996	D	0.834	deleterious	None	None	None	None	N
V/L	0.5849	likely_pathogenic	0.7345	pathogenic	-0.697	Destabilizing	0.835	D	0.617	neutral	D	0.606437769	None	None	N
V/M	0.5406	ambiguous	0.6766	pathogenic	-0.443	Destabilizing	0.996	D	0.679	prob.neutral	None	None	None	None	N
V/N	0.924	likely_pathogenic	0.9601	pathogenic	-0.976	Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	N
V/P	0.7759	likely_pathogenic	0.8886	pathogenic	-0.952	Destabilizing	0.996	D	0.847	deleterious	None	None	None	None	N
V/Q	0.9338	likely_pathogenic	0.9588	pathogenic	-1.103	Destabilizing	0.999	D	0.844	deleterious	None	None	None	None	N
V/R	0.9388	likely_pathogenic	0.9557	pathogenic	-0.776	Destabilizing	0.996	D	0.845	deleterious	None	None	None	None	N
V/S	0.7237	likely_pathogenic	0.8263	pathogenic	-1.421	Destabilizing	0.942	D	0.814	deleterious	None	None	None	None	N
V/T	0.5053	ambiguous	0.6599	pathogenic	-1.275	Destabilizing	0.97	D	0.66	neutral	None	None	None	None	N
V/W	0.9889	likely_pathogenic	0.994	pathogenic	-1.43	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
V/Y	0.9621	likely_pathogenic	0.9782	pathogenic	-1.128	Destabilizing	0.999	D	0.741	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.