TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28186	84781;84782;84783	chr2:178561576;178561575;178561574	chr2:179426303;179426302;179426301
N2AB	26545	79858;79859;79860	chr2:178561576;178561575;178561574	chr2:179426303;179426302;179426301
N2A	25618	77077;77078;77079	chr2:178561576;178561575;178561574	chr2:179426303;179426302;179426301
N2B	19121	57586;57587;57588	chr2:178561576;178561575;178561574	chr2:179426303;179426302;179426301
Novex-1	19246	57961;57962;57963	chr2:178561576;178561575;178561574	chr2:179426303;179426302;179426301
Novex-2	19313	58162;58163;58164	chr2:178561576;178561575;178561574	chr2:179426303;179426302;179426301
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: Fn3-93
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.292
• 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	0.369	N	0.511	0.146	0.476908202251	gnomAD-4.0.0	1.59267E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	2.41663E-04	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	0.9026	likely_pathogenic	0.8956	pathogenic	-1.717	Destabilizing	0.892	D	0.595	neutral	N	0.497034364	None	None	I
V/C	0.9558	likely_pathogenic	0.9608	pathogenic	-1.205	Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	I
V/D	0.9875	likely_pathogenic	0.991	pathogenic	-1.463	Destabilizing	0.996	D	0.868	deleterious	None	None	None	None	I
V/E	0.9677	likely_pathogenic	0.9709	pathogenic	-1.406	Destabilizing	0.994	D	0.861	deleterious	N	0.504885177	None	None	I
V/F	0.8945	likely_pathogenic	0.9007	pathogenic	-1.204	Destabilizing	0.975	D	0.839	deleterious	None	None	None	None	I
V/G	0.9128	likely_pathogenic	0.9253	pathogenic	-2.101	Highly Destabilizing	0.983	D	0.847	deleterious	N	0.516152577	None	None	I
V/H	0.991	likely_pathogenic	0.9936	pathogenic	-1.552	Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	I
V/I	0.0762	likely_benign	0.0778	benign	-0.735	Destabilizing	0.025	N	0.261	neutral	N	0.38444995	None	None	I
V/K	0.98	likely_pathogenic	0.9821	pathogenic	-1.434	Destabilizing	0.987	D	0.86	deleterious	None	None	None	None	I
V/L	0.579	likely_pathogenic	0.613	pathogenic	-0.735	Destabilizing	0.369	N	0.511	neutral	N	0.514382491	None	None	I
V/M	0.6825	likely_pathogenic	0.6988	pathogenic	-0.572	Destabilizing	0.975	D	0.773	deleterious	None	None	None	None	I
V/N	0.927	likely_pathogenic	0.9599	pathogenic	-1.341	Destabilizing	0.996	D	0.861	deleterious	None	None	None	None	I
V/P	0.8705	likely_pathogenic	0.8428	pathogenic	-1.028	Destabilizing	0.996	D	0.873	deleterious	None	None	None	None	I
V/Q	0.9761	likely_pathogenic	0.9783	pathogenic	-1.43	Destabilizing	0.996	D	0.864	deleterious	None	None	None	None	I
V/R	0.9738	likely_pathogenic	0.9765	pathogenic	-0.941	Destabilizing	0.996	D	0.859	deleterious	None	None	None	None	I
V/S	0.9469	likely_pathogenic	0.9532	pathogenic	-1.958	Destabilizing	0.987	D	0.857	deleterious	None	None	None	None	I
V/T	0.8812	likely_pathogenic	0.8823	pathogenic	-1.776	Destabilizing	0.916	D	0.747	deleterious	None	None	None	None	I
V/W	0.9964	likely_pathogenic	0.9968	pathogenic	-1.44	Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	I
V/Y	0.9819	likely_pathogenic	0.9851	pathogenic	-1.139	Destabilizing	0.987	D	0.838	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.