TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32710	98353;98354;98355	chr2:178539937;178539936;178539935	chr2:179404664;179404663;179404662
N2AB	31069	93430;93431;93432	chr2:178539937;178539936;178539935	chr2:179404664;179404663;179404662
N2A	30142	90649;90650;90651	chr2:178539937;178539936;178539935	chr2:179404664;179404663;179404662
N2B	23645	71158;71159;71160	chr2:178539937;178539936;178539935	chr2:179404664;179404663;179404662
Novex-1	23770	71533;71534;71535	chr2:178539937;178539936;178539935	chr2:179404664;179404663;179404662
Novex-2	23837	71734;71735;71736	chr2:178539937;178539936;178539935	chr2:179404664;179404663;179404662
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-155
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.5686
• 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
Y/H	None	None	1.0	D	0.677	0.459	0.530160902827	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
Y/A	0.8083	likely_pathogenic	0.7804	pathogenic	-2.147	Highly Destabilizing	1.0	D	0.655	neutral	None	None	None	None	I
Y/C	0.2858	likely_benign	0.2787	benign	-1.298	Destabilizing	1.0	D	0.72	prob.delet.	D	0.531611175	None	None	I
Y/D	0.7229	likely_pathogenic	0.6978	pathogenic	-0.849	Destabilizing	1.0	D	0.736	prob.delet.	D	0.531611175	None	None	I
Y/E	0.8992	likely_pathogenic	0.8875	pathogenic	-0.724	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
Y/F	0.1319	likely_benign	0.1208	benign	-0.755	Destabilizing	0.999	D	0.631	neutral	N	0.448512576	None	None	I
Y/G	0.7327	likely_pathogenic	0.7217	pathogenic	-2.498	Highly Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
Y/H	0.4314	ambiguous	0.43	ambiguous	-1.029	Destabilizing	1.0	D	0.677	prob.neutral	D	0.531611175	None	None	I
Y/I	0.6439	likely_pathogenic	0.6011	pathogenic	-1.071	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
Y/K	0.8794	likely_pathogenic	0.8701	pathogenic	-1.435	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
Y/L	0.4785	ambiguous	0.4385	ambiguous	-1.071	Destabilizing	0.999	D	0.69	prob.neutral	None	None	None	None	I
Y/M	0.717	likely_pathogenic	0.6723	pathogenic	-0.974	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
Y/N	0.4564	ambiguous	0.4438	ambiguous	-1.906	Destabilizing	1.0	D	0.711	prob.delet.	D	0.531264459	None	None	I
Y/P	0.9372	likely_pathogenic	0.9277	pathogenic	-1.427	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
Y/Q	0.808	likely_pathogenic	0.7963	pathogenic	-1.685	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
Y/R	0.8156	likely_pathogenic	0.8089	pathogenic	-1.199	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
Y/S	0.5743	likely_pathogenic	0.5466	ambiguous	-2.437	Highly Destabilizing	1.0	D	0.695	prob.neutral	N	0.511985265	None	None	I
Y/T	0.7775	likely_pathogenic	0.7447	pathogenic	-2.202	Highly Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	I
Y/V	0.597	likely_pathogenic	0.5582	ambiguous	-1.427	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	I
Y/W	0.5229	ambiguous	0.4726	ambiguous	-0.336	Destabilizing	1.0	D	0.686	prob.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.