TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30980	93163;93164;93165	chr2:178548688;178548687;178548686	chr2:179413415;179413414;179413413
N2AB	29339	88240;88241;88242	chr2:178548688;178548687;178548686	chr2:179413415;179413414;179413413
N2A	28412	85459;85460;85461	chr2:178548688;178548687;178548686	chr2:179413415;179413414;179413413
N2B	21915	65968;65969;65970	chr2:178548688;178548687;178548686	chr2:179413415;179413414;179413413
Novex-1	22040	66343;66344;66345	chr2:178548688;178548687;178548686	chr2:179413415;179413414;179413413
Novex-2	22107	66544;66545;66546	chr2:178548688;178548687;178548686	chr2:179413415;179413414;179413413
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-150
• Domain position: 54
• Structural Position: 137
• Q(SASA): 0.2001
• 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
T/N	None	None	0.994	N	0.564	0.432	0.531922418639	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
T/A	0.1157	likely_benign	0.1092	benign	-1.295	Destabilizing	0.911	D	0.489	neutral	D	0.535217202	None	None	I
T/C	0.436	ambiguous	0.4173	ambiguous	-0.848	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	I
T/D	0.7518	likely_pathogenic	0.7219	pathogenic	-2.006	Highly Destabilizing	0.996	D	0.647	neutral	None	None	None	None	I
T/E	0.5475	ambiguous	0.5242	ambiguous	-1.721	Destabilizing	0.996	D	0.639	neutral	None	None	None	None	I
T/F	0.3406	ambiguous	0.3235	benign	-0.741	Destabilizing	0.998	D	0.724	prob.delet.	None	None	None	None	I
T/G	0.4732	ambiguous	0.439	ambiguous	-1.744	Destabilizing	0.985	D	0.645	neutral	None	None	None	None	I
T/H	0.3773	ambiguous	0.3495	ambiguous	-1.693	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
T/I	0.2207	likely_benign	0.2222	benign	-0.071	Destabilizing	0.606	D	0.37	neutral	N	0.505819802	None	None	I
T/K	0.4787	ambiguous	0.4492	ambiguous	-0.34	Destabilizing	0.996	D	0.642	neutral	None	None	None	None	I
T/L	0.1255	likely_benign	0.1202	benign	-0.071	Destabilizing	0.931	D	0.545	neutral	None	None	None	None	I
T/M	0.0917	likely_benign	0.0906	benign	-0.302	Destabilizing	0.998	D	0.672	neutral	None	None	None	None	I
T/N	0.2712	likely_benign	0.2591	benign	-1.328	Destabilizing	0.994	D	0.564	neutral	N	0.49146059	None	None	I
T/P	0.8249	likely_pathogenic	0.8061	pathogenic	-0.453	Destabilizing	0.997	D	0.678	prob.neutral	D	0.524150381	None	None	I
T/Q	0.3648	ambiguous	0.3401	ambiguous	-0.871	Destabilizing	0.998	D	0.687	prob.neutral	None	None	None	None	I
T/R	0.3758	ambiguous	0.347	ambiguous	-0.833	Destabilizing	0.998	D	0.682	prob.neutral	None	None	None	None	I
T/S	0.152	likely_benign	0.1421	benign	-1.513	Destabilizing	0.659	D	0.396	neutral	N	0.484556308	None	None	I
T/V	0.1613	likely_benign	0.1628	benign	-0.453	Destabilizing	0.469	N	0.392	neutral	None	None	None	None	I
T/W	0.7283	likely_pathogenic	0.7203	pathogenic	-1.051	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	I
T/Y	0.3504	ambiguous	0.3394	benign	-0.639	Destabilizing	0.999	D	0.737	prob.delet.	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.