TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32759	98500;98501;98502	chr2:178539790;178539789;178539788	chr2:179404517;179404516;179404515
N2AB	31118	93577;93578;93579	chr2:178539790;178539789;178539788	chr2:179404517;179404516;179404515
N2A	30191	90796;90797;90798	chr2:178539790;178539789;178539788	chr2:179404517;179404516;179404515
N2B	23694	71305;71306;71307	chr2:178539790;178539789;178539788	chr2:179404517;179404516;179404515
Novex-1	23819	71680;71681;71682	chr2:178539790;178539789;178539788	chr2:179404517;179404516;179404515
Novex-2	23886	71881;71882;71883	chr2:178539790;178539789;178539788	chr2:179404517;179404516;179404515
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-155
• Domain position: 52
• Structural Position: 137
• Q(SASA): 0.2868
• 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
E/K	rs748573833	-0.761	0.999	N	0.581	0.374	0.362960570912	gnomAD-2.1.1	8.04E-06	None	None	None	None	I	None	0	0	None	0	1.11408E-04	None	0	None	0	0	0
E/K	rs748573833	-0.761	0.999	N	0.581	0.374	0.362960570912	gnomAD-4.0.0	3.18233E-06	None	None	None	None	I	None	0	0	None	0	5.54539E-05	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
E/A	0.6374	likely_pathogenic	0.616	pathogenic	-0.569	Destabilizing	0.999	D	0.647	neutral	N	0.508315815	None	None	I
E/C	0.9729	likely_pathogenic	0.9706	pathogenic	-0.531	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
E/D	0.6808	likely_pathogenic	0.6794	pathogenic	-1.433	Destabilizing	0.999	D	0.524	neutral	N	0.50883589	None	None	I
E/F	0.9803	likely_pathogenic	0.9804	pathogenic	-0.498	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	I
E/G	0.8061	likely_pathogenic	0.7913	pathogenic	-0.945	Destabilizing	1.0	D	0.715	prob.delet.	N	0.500120406	None	None	I
E/H	0.9117	likely_pathogenic	0.906	pathogenic	-1.055	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
E/I	0.8638	likely_pathogenic	0.8497	pathogenic	0.454	Stabilizing	1.0	D	0.852	deleterious	None	None	None	None	I
E/K	0.8037	likely_pathogenic	0.7624	pathogenic	-1.05	Destabilizing	0.999	D	0.581	neutral	N	0.471797655	None	None	I
E/L	0.9232	likely_pathogenic	0.9145	pathogenic	0.454	Stabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
E/M	0.8718	likely_pathogenic	0.8596	pathogenic	0.952	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
E/N	0.8726	likely_pathogenic	0.8635	pathogenic	-1.323	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	I
E/P	0.9985	likely_pathogenic	0.9981	pathogenic	0.136	Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
E/Q	0.4416	ambiguous	0.4163	ambiguous	-1.109	Destabilizing	1.0	D	0.647	neutral	N	0.473837882	None	None	I
E/R	0.8747	likely_pathogenic	0.8557	pathogenic	-1.02	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	I
E/S	0.6524	likely_pathogenic	0.6461	pathogenic	-1.714	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	I
E/T	0.7083	likely_pathogenic	0.7029	pathogenic	-1.401	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
E/V	0.6871	likely_pathogenic	0.6624	pathogenic	0.136	Stabilizing	1.0	D	0.793	deleterious	N	0.423179775	None	None	I
E/W	0.9953	likely_pathogenic	0.9952	pathogenic	-0.616	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	I
E/Y	0.9693	likely_pathogenic	0.9666	pathogenic	-0.363	Destabilizing	1.0	D	0.829	deleterious	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.