TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28011	84256;84257;84258	chr2:178562101;178562100;178562099	chr2:179426828;179426827;179426826
N2AB	26370	79333;79334;79335	chr2:178562101;178562100;178562099	chr2:179426828;179426827;179426826
N2A	25443	76552;76553;76554	chr2:178562101;178562100;178562099	chr2:179426828;179426827;179426826
N2B	18946	57061;57062;57063	chr2:178562101;178562100;178562099	chr2:179426828;179426827;179426826
Novex-1	19071	57436;57437;57438	chr2:178562101;178562100;178562099	chr2:179426828;179426827;179426826
Novex-2	19138	57637;57638;57639	chr2:178562101;178562100;178562099	chr2:179426828;179426827;179426826
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-142
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.2669
• 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/L	None	None	0.156	D	0.373	0.111	0.393623145366	gnomAD-4.0.0	1.36889E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99614E-07	1.15996E-05	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	0.2404	likely_benign	0.2792	benign	-1.525	Destabilizing	0.008	N	0.291	neutral	D	0.525501641	None	None	N
V/C	0.6443	likely_pathogenic	0.6835	pathogenic	-1.419	Destabilizing	0.989	D	0.585	neutral	None	None	None	None	N
V/D	0.6975	likely_pathogenic	0.7664	pathogenic	-0.633	Destabilizing	0.949	D	0.713	prob.delet.	N	0.501971203	None	None	N
V/E	0.5879	likely_pathogenic	0.6321	pathogenic	-0.584	Destabilizing	0.923	D	0.661	neutral	None	None	None	None	N
V/F	0.1315	likely_benign	0.164	benign	-1.163	Destabilizing	0.901	D	0.603	neutral	N	0.517863592	None	None	N
V/G	0.3473	ambiguous	0.4325	ambiguous	-1.883	Destabilizing	0.82	D	0.665	neutral	N	0.515453875	None	None	N
V/H	0.6551	likely_pathogenic	0.7168	pathogenic	-1.305	Destabilizing	0.996	D	0.717	prob.delet.	None	None	None	None	N
V/I	0.0764	likely_benign	0.073	benign	-0.627	Destabilizing	0.008	N	0.213	neutral	N	0.463103601	None	None	N
V/K	0.5362	ambiguous	0.5932	pathogenic	-1.039	Destabilizing	0.923	D	0.659	neutral	None	None	None	None	N
V/L	0.2485	likely_benign	0.2628	benign	-0.627	Destabilizing	0.156	N	0.373	neutral	D	0.526539004	None	None	N
V/M	0.1713	likely_benign	0.1839	benign	-0.713	Destabilizing	0.923	D	0.493	neutral	None	None	None	None	N
V/N	0.5106	ambiguous	0.5585	ambiguous	-0.952	Destabilizing	0.961	D	0.721	prob.delet.	None	None	None	None	N
V/P	0.89	likely_pathogenic	0.9372	pathogenic	-0.892	Destabilizing	0.961	D	0.667	neutral	None	None	None	None	N
V/Q	0.508	ambiguous	0.5624	ambiguous	-1.003	Destabilizing	0.961	D	0.679	prob.neutral	None	None	None	None	N
V/R	0.4489	ambiguous	0.5352	ambiguous	-0.68	Destabilizing	0.923	D	0.718	prob.delet.	None	None	None	None	N
V/S	0.3374	likely_benign	0.3859	ambiguous	-1.669	Destabilizing	0.858	D	0.621	neutral	None	None	None	None	N
V/T	0.2424	likely_benign	0.2629	benign	-1.472	Destabilizing	0.775	D	0.455	neutral	None	None	None	None	N
V/W	0.7561	likely_pathogenic	0.8163	pathogenic	-1.271	Destabilizing	0.996	D	0.684	prob.neutral	None	None	None	None	N
V/Y	0.4609	ambiguous	0.5279	ambiguous	-0.974	Destabilizing	0.961	D	0.604	neutral	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.