TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28435	85528;85529;85530	chr2:178560829;178560828;178560827	chr2:179425556;179425555;179425554
N2AB	26794	80605;80606;80607	chr2:178560829;178560828;178560827	chr2:179425556;179425555;179425554
N2A	25867	77824;77825;77826	chr2:178560829;178560828;178560827	chr2:179425556;179425555;179425554
N2B	19370	58333;58334;58335	chr2:178560829;178560828;178560827	chr2:179425556;179425555;179425554
Novex-1	19495	58708;58709;58710	chr2:178560829;178560828;178560827	chr2:179425556;179425555;179425554
Novex-2	19562	58909;58910;58911	chr2:178560829;178560828;178560827	chr2:179425556;179425555;179425554
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-143
• Domain position: 78
• Structural Position: 162
• Q(SASA): 0.9265
• 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/A	None	None	0.025	N	0.322	0.203	None	gnomAD-4.0.0	2.05282E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	4.97051E-05

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	0.2345	likely_benign	0.2479	benign	-0.357	Destabilizing	0.025	N	0.322	neutral	N	0.505331438	None	None	I
V/C	0.85	likely_pathogenic	0.8615	pathogenic	-0.816	Destabilizing	0.997	D	0.536	neutral	None	None	None	None	I
V/D	0.5388	ambiguous	0.5959	pathogenic	-0.348	Destabilizing	0.983	D	0.623	neutral	N	0.495250517	None	None	I
V/E	0.4877	ambiguous	0.5419	ambiguous	-0.467	Destabilizing	0.975	D	0.547	neutral	None	None	None	None	I
V/F	0.3171	likely_benign	0.3386	benign	-0.751	Destabilizing	0.983	D	0.528	neutral	N	0.484389337	None	None	I
V/G	0.3816	ambiguous	0.3968	ambiguous	-0.41	Destabilizing	0.935	D	0.519	neutral	D	0.534307551	None	None	I
V/H	0.763	likely_pathogenic	0.7805	pathogenic	-0.041	Destabilizing	0.999	D	0.646	neutral	None	None	None	None	I
V/I	0.0945	likely_benign	0.0954	benign	-0.359	Destabilizing	0.773	D	0.427	neutral	N	0.485534956	None	None	I
V/K	0.5547	ambiguous	0.5991	pathogenic	-0.39	Destabilizing	0.975	D	0.551	neutral	None	None	None	None	I
V/L	0.3552	ambiguous	0.3692	ambiguous	-0.359	Destabilizing	0.63	D	0.425	neutral	N	0.515895148	None	None	I
V/M	0.2583	likely_benign	0.2609	benign	-0.561	Destabilizing	0.996	D	0.526	neutral	None	None	None	None	I
V/N	0.4667	ambiguous	0.4846	ambiguous	-0.204	Destabilizing	0.987	D	0.643	neutral	None	None	None	None	I
V/P	0.5316	ambiguous	0.5306	ambiguous	-0.331	Destabilizing	0.987	D	0.568	neutral	None	None	None	None	I
V/Q	0.5294	ambiguous	0.5643	pathogenic	-0.416	Destabilizing	0.987	D	0.589	neutral	None	None	None	None	I
V/R	0.4807	ambiguous	0.519	ambiguous	0.055	Stabilizing	0.987	D	0.644	neutral	None	None	None	None	I
V/S	0.3481	ambiguous	0.3618	ambiguous	-0.509	Destabilizing	0.95	D	0.462	neutral	None	None	None	None	I
V/T	0.282	likely_benign	0.2917	benign	-0.537	Destabilizing	0.916	D	0.455	neutral	None	None	None	None	I
V/W	0.9278	likely_pathogenic	0.9321	pathogenic	-0.806	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	I
V/Y	0.725	likely_pathogenic	0.7588	pathogenic	-0.533	Destabilizing	0.996	D	0.527	neutral	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.