TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31625	95098;95099;95100	chr2:178546458;178546457;178546456	chr2:179411185;179411184;179411183
N2AB	29984	90175;90176;90177	chr2:178546458;178546457;178546456	chr2:179411185;179411184;179411183
N2A	29057	87394;87395;87396	chr2:178546458;178546457;178546456	chr2:179411185;179411184;179411183
N2B	22560	67903;67904;67905	chr2:178546458;178546457;178546456	chr2:179411185;179411184;179411183
Novex-1	22685	68278;68279;68280	chr2:178546458;178546457;178546456	chr2:179411185;179411184;179411183
Novex-2	22752	68479;68480;68481	chr2:178546458;178546457;178546456	chr2:179411185;179411184;179411183
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-152
• Domain position: 5
• Structural Position: 13
• Q(SASA): 0.272
• 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/I	rs1697179878	None	0.17	N	0.229	0.144	0.464098490096	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/I	rs1697179878	None	0.17	N	0.229	0.144	0.464098490096	gnomAD-4.0.0	6.57358E-06	None	None	None	None	I	None	2.41394E-05	0	None	0	0	None	0	0	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	0.5479	ambiguous	0.5612	ambiguous	-0.903	Destabilizing	0.939	D	0.457	neutral	N	0.490953611	None	None	I
V/C	0.8664	likely_pathogenic	0.8647	pathogenic	-0.97	Destabilizing	0.999	D	0.582	neutral	None	None	None	None	I
V/D	0.9103	likely_pathogenic	0.9113	pathogenic	-0.332	Destabilizing	0.997	D	0.732	prob.delet.	D	0.533495678	None	None	I
V/E	0.7861	likely_pathogenic	0.791	pathogenic	-0.339	Destabilizing	0.998	D	0.669	neutral	None	None	None	None	I
V/F	0.2976	likely_benign	0.3035	benign	-0.585	Destabilizing	0.982	D	0.621	neutral	N	0.505983674	None	None	I
V/G	0.6959	likely_pathogenic	0.7033	pathogenic	-1.183	Destabilizing	0.997	D	0.703	prob.neutral	D	0.532735209	None	None	I
V/H	0.8602	likely_pathogenic	0.8657	pathogenic	-0.582	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	I
V/I	0.0873	likely_benign	0.088	benign	-0.26	Destabilizing	0.17	N	0.229	neutral	N	0.446886141	None	None	I
V/K	0.7667	likely_pathogenic	0.7692	pathogenic	-0.837	Destabilizing	0.993	D	0.668	neutral	None	None	None	None	I
V/L	0.1996	likely_benign	0.2009	benign	-0.26	Destabilizing	0.046	N	0.284	neutral	N	0.494215941	None	None	I
V/M	0.2415	likely_benign	0.2532	benign	-0.447	Destabilizing	0.986	D	0.527	neutral	None	None	None	None	I
V/N	0.8317	likely_pathogenic	0.8317	pathogenic	-0.744	Destabilizing	0.998	D	0.728	prob.delet.	None	None	None	None	I
V/P	0.9147	likely_pathogenic	0.9159	pathogenic	-0.438	Destabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	I
V/Q	0.6937	likely_pathogenic	0.7007	pathogenic	-0.834	Destabilizing	0.998	D	0.675	prob.neutral	None	None	None	None	I
V/R	0.7274	likely_pathogenic	0.7353	pathogenic	-0.41	Destabilizing	0.993	D	0.727	prob.delet.	None	None	None	None	I
V/S	0.7482	likely_pathogenic	0.7586	pathogenic	-1.289	Destabilizing	0.993	D	0.646	neutral	None	None	None	None	I
V/T	0.6053	likely_pathogenic	0.611	pathogenic	-1.17	Destabilizing	0.976	D	0.481	neutral	None	None	None	None	I
V/W	0.924	likely_pathogenic	0.9248	pathogenic	-0.729	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	I
V/Y	0.7713	likely_pathogenic	0.7754	pathogenic	-0.428	Destabilizing	0.993	D	0.629	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.