TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16937	51034;51035;51036	chr2:178611420;178611419;178611418	chr2:179476147;179476146;179476145
N2AB	15296	46111;46112;46113	chr2:178611420;178611419;178611418	chr2:179476147;179476146;179476145
N2A	14369	43330;43331;43332	chr2:178611420;178611419;178611418	chr2:179476147;179476146;179476145
N2B	7872	23839;23840;23841	chr2:178611420;178611419;178611418	chr2:179476147;179476146;179476145
Novex-1	7997	24214;24215;24216	chr2:178611420;178611419;178611418	chr2:179476147;179476146;179476145
Novex-2	8064	24415;24416;24417	chr2:178611420;178611419;178611418	chr2:179476147;179476146;179476145
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-11
• Domain position: 86
• Structural Position: 118
• Q(SASA): 0.074
• 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
S/R	rs780845171	-1.036	1.0	D	0.791	0.435	0.306695030598	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	5.63E-05	None	0	None	0	0	0
S/R	rs780845171	-1.036	1.0	D	0.791	0.435	0.306695030598	gnomAD-4.0.0	6.16119E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	9.2773E-05	1.65799E-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
S/A	0.594	likely_pathogenic	0.611	pathogenic	-0.899	Destabilizing	0.98	D	0.673	neutral	None	None	None	None	N
S/C	0.8467	likely_pathogenic	0.8794	pathogenic	-0.964	Destabilizing	1.0	D	0.75	deleterious	D	0.72538889	None	None	N
S/D	0.9905	likely_pathogenic	0.9941	pathogenic	-1.735	Destabilizing	0.996	D	0.737	prob.delet.	None	None	None	None	N
S/E	0.996	likely_pathogenic	0.9975	pathogenic	-1.618	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
S/F	0.9977	likely_pathogenic	0.9988	pathogenic	-0.661	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
S/G	0.1797	likely_benign	0.2128	benign	-1.217	Destabilizing	0.104	N	0.426	neutral	N	0.443608299	None	None	N
S/H	0.9942	likely_pathogenic	0.9964	pathogenic	-1.529	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
S/I	0.9965	likely_pathogenic	0.9982	pathogenic	-0.122	Destabilizing	0.999	D	0.853	deleterious	D	0.724603427	None	None	N
S/K	0.9994	likely_pathogenic	0.9997	pathogenic	-0.944	Destabilizing	0.996	D	0.752	deleterious	None	None	None	None	N
S/L	0.9794	likely_pathogenic	0.989	pathogenic	-0.122	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
S/M	0.9886	likely_pathogenic	0.993	pathogenic	-0.185	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
S/N	0.9728	likely_pathogenic	0.9841	pathogenic	-1.341	Destabilizing	0.994	D	0.735	prob.delet.	D	0.723308633	None	None	N
S/P	0.9951	likely_pathogenic	0.9973	pathogenic	-0.349	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
S/Q	0.9955	likely_pathogenic	0.9972	pathogenic	-1.293	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
S/R	0.9986	likely_pathogenic	0.9992	pathogenic	-0.995	Destabilizing	1.0	D	0.791	deleterious	D	0.686829537	None	None	N
S/T	0.8164	likely_pathogenic	0.8748	pathogenic	-1.08	Destabilizing	0.994	D	0.701	prob.neutral	D	0.720975846	None	None	N
S/V	0.9934	likely_pathogenic	0.9963	pathogenic	-0.349	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
S/W	0.9969	likely_pathogenic	0.9985	pathogenic	-0.855	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
S/Y	0.9961	likely_pathogenic	0.9978	pathogenic	-0.503	Destabilizing	1.0	D	0.847	deleterious	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.