TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34323	103192;103193;103194	chr2:178533648;178533647;178533646	chr2:179398375;179398374;179398373
N2AB	32682	98269;98270;98271	chr2:178533648;178533647;178533646	chr2:179398375;179398374;179398373
N2A	31755	95488;95489;95490	chr2:178533648;178533647;178533646	chr2:179398375;179398374;179398373
N2B	25258	75997;75998;75999	chr2:178533648;178533647;178533646	chr2:179398375;179398374;179398373
Novex-1	25383	76372;76373;76374	chr2:178533648;178533647;178533646	chr2:179398375;179398374;179398373
Novex-2	25450	76573;76574;76575	chr2:178533648;178533647;178533646	chr2:179398375;179398374;179398373
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-161
• Domain position: 66
• Structural Position: 144
• Q(SASA): 0.0908
• 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/G	rs1307866503	None	0.995	D	0.715	0.7	0.867032782884	gnomAD-4.0.0	1.59099E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85763E-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	0.6069	likely_pathogenic	0.5874	pathogenic	-2.099	Highly Destabilizing	0.78	D	0.564	neutral	N	0.456638988	None	None	N
V/C	0.9267	likely_pathogenic	0.9265	pathogenic	-2.423	Highly Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
V/D	0.9912	likely_pathogenic	0.9898	pathogenic	-3.298	Highly Destabilizing	0.995	D	0.722	prob.delet.	D	0.535270105	None	None	N
V/E	0.9799	likely_pathogenic	0.9782	pathogenic	-3.199	Highly Destabilizing	0.996	D	0.676	prob.neutral	None	None	None	None	N
V/F	0.8849	likely_pathogenic	0.8906	pathogenic	-1.575	Destabilizing	0.968	D	0.709	prob.delet.	N	0.516405381	None	None	N
V/G	0.8767	likely_pathogenic	0.8657	pathogenic	-2.475	Highly Destabilizing	0.995	D	0.715	prob.delet.	D	0.535016615	None	None	N
V/H	0.9954	likely_pathogenic	0.9952	pathogenic	-1.881	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	N
V/I	0.1024	likely_benign	0.1123	benign	-1.096	Destabilizing	0.64	D	0.488	neutral	N	0.506529091	None	None	N
V/K	0.985	likely_pathogenic	0.9811	pathogenic	-1.935	Destabilizing	0.988	D	0.675	prob.neutral	None	None	None	None	N
V/L	0.3629	ambiguous	0.3547	ambiguous	-1.096	Destabilizing	0.004	N	0.262	neutral	N	0.472862021	None	None	N
V/M	0.5313	ambiguous	0.5108	ambiguous	-1.312	Destabilizing	0.976	D	0.649	neutral	None	None	None	None	N
V/N	0.965	likely_pathogenic	0.9591	pathogenic	-2.224	Highly Destabilizing	0.996	D	0.722	prob.delet.	None	None	None	None	N
V/P	0.9503	likely_pathogenic	0.938	pathogenic	-1.404	Destabilizing	0.996	D	0.679	prob.neutral	None	None	None	None	N
V/Q	0.9811	likely_pathogenic	0.9768	pathogenic	-2.33	Highly Destabilizing	0.996	D	0.665	neutral	None	None	None	None	N
V/R	0.9775	likely_pathogenic	0.9744	pathogenic	-1.435	Destabilizing	0.988	D	0.723	prob.delet.	None	None	None	None	N
V/S	0.8953	likely_pathogenic	0.8922	pathogenic	-2.714	Highly Destabilizing	0.988	D	0.681	prob.neutral	None	None	None	None	N
V/T	0.6701	likely_pathogenic	0.5955	pathogenic	-2.5	Highly Destabilizing	0.959	D	0.601	neutral	None	None	None	None	N
V/W	0.9984	likely_pathogenic	0.9986	pathogenic	-1.879	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
V/Y	0.9922	likely_pathogenic	0.9933	pathogenic	-1.58	Destabilizing	0.996	D	0.717	prob.delet.	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.