TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28327	85204;85205;85206	chr2:178561153;178561152;178561151	chr2:179425880;179425879;179425878
N2AB	26686	80281;80282;80283	chr2:178561153;178561152;178561151	chr2:179425880;179425879;179425878
N2A	25759	77500;77501;77502	chr2:178561153;178561152;178561151	chr2:179425880;179425879;179425878
N2B	19262	58009;58010;58011	chr2:178561153;178561152;178561151	chr2:179425880;179425879;179425878
Novex-1	19387	58384;58385;58386	chr2:178561153;178561152;178561151	chr2:179425880;179425879;179425878
Novex-2	19454	58585;58586;58587	chr2:178561153;178561152;178561151	chr2:179425880;179425879;179425878
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: Fn3-94
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0789
• 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	None	None	0.37	N	0.234	0.238	0.534814951121	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.8037	likely_pathogenic	0.7366	pathogenic	-2.72	Highly Destabilizing	0.978	D	0.596	neutral	D	0.552973194	None	None	N
V/C	0.9413	likely_pathogenic	0.9377	pathogenic	-1.88	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
V/D	0.9986	likely_pathogenic	0.9977	pathogenic	-3.247	Highly Destabilizing	0.999	D	0.848	deleterious	D	0.654093119	None	None	N
V/E	0.9968	likely_pathogenic	0.9947	pathogenic	-2.943	Highly Destabilizing	0.999	D	0.808	deleterious	None	None	None	None	N
V/F	0.9514	likely_pathogenic	0.9335	pathogenic	-1.402	Destabilizing	0.997	D	0.712	prob.delet.	D	0.5850671	None	None	N
V/G	0.9494	likely_pathogenic	0.92	pathogenic	-3.263	Highly Destabilizing	0.999	D	0.836	deleterious	D	0.654093119	None	None	N
V/H	0.999	likely_pathogenic	0.9986	pathogenic	-2.925	Highly Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
V/I	0.1125	likely_benign	0.1042	benign	-1.109	Destabilizing	0.37	N	0.234	neutral	N	0.518575668	None	None	N
V/K	0.998	likely_pathogenic	0.9972	pathogenic	-1.985	Destabilizing	0.999	D	0.812	deleterious	None	None	None	None	N
V/L	0.7762	likely_pathogenic	0.7209	pathogenic	-1.109	Destabilizing	0.9	D	0.515	neutral	D	0.525052662	None	None	N
V/M	0.8682	likely_pathogenic	0.8306	pathogenic	-1.436	Destabilizing	0.998	D	0.682	prob.neutral	None	None	None	None	N
V/N	0.9932	likely_pathogenic	0.989	pathogenic	-2.616	Highly Destabilizing	0.999	D	0.85	deleterious	None	None	None	None	N
V/P	0.9958	likely_pathogenic	0.994	pathogenic	-1.635	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
V/Q	0.9961	likely_pathogenic	0.9942	pathogenic	-2.257	Highly Destabilizing	0.999	D	0.836	deleterious	None	None	None	None	N
V/R	0.9941	likely_pathogenic	0.9919	pathogenic	-2.062	Highly Destabilizing	0.999	D	0.856	deleterious	None	None	None	None	N
V/S	0.9575	likely_pathogenic	0.9329	pathogenic	-3.064	Highly Destabilizing	0.999	D	0.81	deleterious	None	None	None	None	N
V/T	0.9176	likely_pathogenic	0.8905	pathogenic	-2.623	Highly Destabilizing	0.992	D	0.653	neutral	None	None	None	None	N
V/W	0.9995	likely_pathogenic	0.9992	pathogenic	-1.803	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
V/Y	0.9951	likely_pathogenic	0.9934	pathogenic	-1.684	Destabilizing	0.999	D	0.728	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.