TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28000	84223;84224;84225	chr2:178562134;178562133;178562132	chr2:179426861;179426860;179426859
N2AB	26359	79300;79301;79302	chr2:178562134;178562133;178562132	chr2:179426861;179426860;179426859
N2A	25432	76519;76520;76521	chr2:178562134;178562133;178562132	chr2:179426861;179426860;179426859
N2B	18935	57028;57029;57030	chr2:178562134;178562133;178562132	chr2:179426861;179426860;179426859
Novex-1	19060	57403;57404;57405	chr2:178562134;178562133;178562132	chr2:179426861;179426860;179426859
Novex-2	19127	57604;57605;57606	chr2:178562134;178562133;178562132	chr2:179426861;179426860;179426859
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-142
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.534
• 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
G/C	rs1335831025	-0.944	1.0	D	0.744	0.541	0.715437530537	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
G/C	rs1335831025	-0.944	1.0	D	0.744	0.541	0.715437530537	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
G/C	rs1335831025	-0.944	1.0	D	0.744	0.541	0.715437530537	gnomAD-4.0.0	1.23993E-06	None	None	None	None	N	None	0	3.33812E-05	None	0	0	None	0	0	0	0	0
G/D	rs374151070	-0.634	0.999	N	0.712	0.345	0.30921473904	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	5.64E-05	None	0	None	0	0	0
G/D	rs374151070	-0.634	0.999	N	0.712	0.345	0.30921473904	gnomAD-4.0.0	4.8013E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25002E-06	0	0
G/S	rs1335831025	-0.459	0.995	N	0.681	0.495	0.353336612579	gnomAD-2.1.1	1.22E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.69E-05	0
G/S	rs1335831025	-0.459	0.995	N	0.681	0.495	0.353336612579	gnomAD-4.0.0	9.58319E-06	None	None	None	None	N	None	0	2.23994E-05	None	0	0	None	0	0	1.07961E-05	0	1.65744E-05
G/V	rs374151070	-0.232	0.995	D	0.733	0.436	None	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	6.52E-05	0	None	0	0	None	0	None	0	0	0
G/V	rs374151070	-0.232	0.995	D	0.733	0.436	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
G/V	rs374151070	-0.232	0.995	D	0.733	0.436	None	gnomAD-4.0.0	6.5722E-06	None	None	None	None	N	None	2.41301E-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
G/A	0.3038	likely_benign	0.2502	benign	-0.353	Destabilizing	0.45	N	0.523	neutral	N	0.491141653	None	None	N
G/C	0.3143	likely_benign	0.2683	benign	-0.884	Destabilizing	1.0	D	0.744	deleterious	D	0.526389112	None	None	N
G/D	0.2208	likely_benign	0.1925	benign	-0.787	Destabilizing	0.999	D	0.712	prob.delet.	N	0.496465947	None	None	N
G/E	0.2817	likely_benign	0.2461	benign	-0.965	Destabilizing	0.998	D	0.717	prob.delet.	None	None	None	None	N
G/F	0.7397	likely_pathogenic	0.677	pathogenic	-1.146	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
G/H	0.3939	ambiguous	0.3391	benign	-0.519	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
G/I	0.6073	likely_pathogenic	0.5256	ambiguous	-0.553	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
G/K	0.392	ambiguous	0.3311	benign	-0.788	Destabilizing	0.998	D	0.716	prob.delet.	None	None	None	None	N
G/L	0.6788	likely_pathogenic	0.6048	pathogenic	-0.553	Destabilizing	0.996	D	0.733	prob.delet.	None	None	None	None	N
G/M	0.6738	likely_pathogenic	0.5993	pathogenic	-0.459	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
G/N	0.2459	likely_benign	0.1986	benign	-0.448	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
G/P	0.9723	likely_pathogenic	0.9617	pathogenic	-0.456	Destabilizing	0.999	D	0.724	prob.delet.	None	None	None	None	N
G/Q	0.3195	likely_benign	0.2709	benign	-0.803	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
G/R	0.2862	likely_benign	0.2611	benign	-0.275	Destabilizing	0.999	D	0.735	prob.delet.	N	0.513600774	None	None	N
G/S	0.1374	likely_benign	0.1212	benign	-0.562	Destabilizing	0.995	D	0.681	prob.neutral	N	0.494229072	None	None	N
G/T	0.3425	ambiguous	0.281	benign	-0.682	Destabilizing	0.998	D	0.714	prob.delet.	None	None	None	None	N
G/V	0.5194	ambiguous	0.4479	ambiguous	-0.456	Destabilizing	0.995	D	0.733	prob.delet.	D	0.526389112	None	None	N
G/W	0.5808	likely_pathogenic	0.5257	ambiguous	-1.245	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
G/Y	0.5814	likely_pathogenic	0.5024	ambiguous	-0.915	Destabilizing	1.0	D	0.757	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.