TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6741	20446;20447;20448	chr2:178727144;178727143;178727142	chr2:179591871;179591870;179591869
N2AB	6424	19495;19496;19497	chr2:178727144;178727143;178727142	chr2:179591871;179591870;179591869
N2A	5497	16714;16715;16716	chr2:178727144;178727143;178727142	chr2:179591871;179591870;179591869
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-51
• Domain position: 75
• Structural Position: 157
• Q(SASA): 0.361
• 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
E/G	rs1380825036	-1.96	0.999	N	0.718	0.341	0.589461000006	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14811E-04	0	None	0	0	None	0	None	0	0	0
E/G	rs1380825036	-1.96	0.999	N	0.718	0.341	0.589461000006	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
E/G	rs1380825036	-1.96	0.999	N	0.718	0.341	0.589461000006	gnomAD-4.0.0	6.5735E-06	None	None	None	None	N	None	2.41243E-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
E/A	0.4094	ambiguous	0.4002	ambiguous	-1.1	Destabilizing	0.975	D	0.628	neutral	N	0.496163716	None	None	N
E/C	0.9707	likely_pathogenic	0.9647	pathogenic	-0.602	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
E/D	0.455	ambiguous	0.4399	ambiguous	-1.391	Destabilizing	0.912	D	0.557	neutral	N	0.506140896	None	None	N
E/F	0.9092	likely_pathogenic	0.9029	pathogenic	-0.739	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
E/G	0.6192	likely_pathogenic	0.6074	pathogenic	-1.49	Destabilizing	0.999	D	0.718	prob.delet.	N	0.506647875	None	None	N
E/H	0.6768	likely_pathogenic	0.6703	pathogenic	-1.0	Destabilizing	1.0	D	0.626	neutral	None	None	None	None	N
E/I	0.4916	ambiguous	0.4814	ambiguous	-0.017	Destabilizing	0.988	D	0.744	deleterious	None	None	None	None	N
E/K	0.1978	likely_benign	0.214	benign	-0.781	Destabilizing	0.496	N	0.418	neutral	N	0.498058749	None	None	N
E/L	0.6387	likely_pathogenic	0.6322	pathogenic	-0.017	Destabilizing	0.958	D	0.712	prob.delet.	None	None	None	None	N
E/M	0.6176	likely_pathogenic	0.6164	pathogenic	0.568	Stabilizing	0.995	D	0.763	deleterious	None	None	None	None	N
E/N	0.6235	likely_pathogenic	0.6173	pathogenic	-1.214	Destabilizing	0.993	D	0.591	neutral	None	None	None	None	N
E/P	0.9966	likely_pathogenic	0.9963	pathogenic	-0.358	Destabilizing	0.993	D	0.736	prob.delet.	None	None	None	None	N
E/Q	0.1987	likely_benign	0.2031	benign	-1.063	Destabilizing	0.995	D	0.594	neutral	N	0.498405466	None	None	N
E/R	0.3932	ambiguous	0.3978	ambiguous	-0.615	Destabilizing	0.994	D	0.595	neutral	None	None	None	None	N
E/S	0.4874	ambiguous	0.4762	ambiguous	-1.662	Destabilizing	0.981	D	0.575	neutral	None	None	None	None	N
E/T	0.4445	ambiguous	0.426	ambiguous	-1.316	Destabilizing	0.986	D	0.662	neutral	None	None	None	None	N
E/V	0.3224	likely_benign	0.3049	benign	-0.358	Destabilizing	0.431	N	0.567	neutral	N	0.488689904	None	None	N
E/W	0.9764	likely_pathogenic	0.9753	pathogenic	-0.557	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
E/Y	0.8657	likely_pathogenic	0.8562	pathogenic	-0.465	Destabilizing	1.0	D	0.781	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.