TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7035	21328;21329;21330	chr2:178724272;178724271;178724270	chr2:179588999;179588998;179588997
N2AB	6718	20377;20378;20379	chr2:178724272;178724271;178724270	chr2:179588999;179588998;179588997
N2A	5791	17596;17597;17598	chr2:178724272;178724271;178724270	chr2:179588999;179588998;179588997
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-54
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.1232
• 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	rs1553913782	None	0.001	N	0.256	0.045	0.194818534648	gnomAD-4.0.0	8.21593E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.07986E-05	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	0.6303	likely_pathogenic	0.5447	ambiguous	-2.248	Highly Destabilizing	0.22	N	0.679	prob.neutral	N	0.479172556	None	None	N
V/C	0.9611	likely_pathogenic	0.9437	pathogenic	-1.98	Destabilizing	0.968	D	0.776	deleterious	None	None	None	None	N
V/D	0.9912	likely_pathogenic	0.9844	pathogenic	-2.845	Highly Destabilizing	0.667	D	0.857	deleterious	N	0.479679535	None	None	N
V/E	0.973	likely_pathogenic	0.9564	pathogenic	-2.676	Highly Destabilizing	0.726	D	0.842	deleterious	None	None	None	None	N
V/F	0.4941	ambiguous	0.3802	ambiguous	-1.473	Destabilizing	0.497	N	0.799	deleterious	N	0.504333282	None	None	N
V/G	0.8641	likely_pathogenic	0.8069	pathogenic	-2.752	Highly Destabilizing	0.667	D	0.855	deleterious	N	0.479679535	None	None	N
V/H	0.9912	likely_pathogenic	0.9839	pathogenic	-2.385	Highly Destabilizing	0.968	D	0.854	deleterious	None	None	None	None	N
V/I	0.0827	likely_benign	0.0785	benign	-0.859	Destabilizing	0.001	N	0.256	neutral	N	0.452344236	None	None	N
V/K	0.979	likely_pathogenic	0.9663	pathogenic	-1.904	Destabilizing	0.726	D	0.84	deleterious	None	None	None	None	N
V/L	0.2456	likely_benign	0.1721	benign	-0.859	Destabilizing	None	N	0.314	neutral	N	0.380291271	None	None	N
V/M	0.3387	likely_benign	0.2444	benign	-0.895	Destabilizing	0.567	D	0.71	prob.delet.	None	None	None	None	N
V/N	0.9768	likely_pathogenic	0.96	pathogenic	-2.142	Highly Destabilizing	0.89	D	0.854	deleterious	None	None	None	None	N
V/P	0.9766	likely_pathogenic	0.9547	pathogenic	-1.294	Destabilizing	0.89	D	0.826	deleterious	None	None	None	None	N
V/Q	0.9696	likely_pathogenic	0.9484	pathogenic	-2.081	Highly Destabilizing	0.89	D	0.836	deleterious	None	None	None	None	N
V/R	0.9608	likely_pathogenic	0.9395	pathogenic	-1.583	Destabilizing	0.726	D	0.853	deleterious	None	None	None	None	N
V/S	0.9189	likely_pathogenic	0.8742	pathogenic	-2.772	Highly Destabilizing	0.726	D	0.825	deleterious	None	None	None	None	N
V/T	0.7212	likely_pathogenic	0.6326	pathogenic	-2.465	Highly Destabilizing	0.272	N	0.71	prob.delet.	None	None	None	None	N
V/W	0.981	likely_pathogenic	0.9618	pathogenic	-1.922	Destabilizing	0.968	D	0.85	deleterious	None	None	None	None	N
V/Y	0.961	likely_pathogenic	0.9297	pathogenic	-1.592	Destabilizing	0.726	D	0.778	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.