TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26963	81112;81113;81114	chr2:178565245;178565244;178565243	chr2:179429972;179429971;179429970
N2AB	25322	76189;76190;76191	chr2:178565245;178565244;178565243	chr2:179429972;179429971;179429970
N2A	24395	73408;73409;73410	chr2:178565245;178565244;178565243	chr2:179429972;179429971;179429970
N2B	17898	53917;53918;53919	chr2:178565245;178565244;178565243	chr2:179429972;179429971;179429970
Novex-1	18023	54292;54293;54294	chr2:178565245;178565244;178565243	chr2:179429972;179429971;179429970
Novex-2	18090	54493;54494;54495	chr2:178565245;178565244;178565243	chr2:179429972;179429971;179429970
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-139
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.1387
• 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/D	rs1705288214	None	0.904	N	0.602	0.241	0.455173453901	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/D	rs1705288214	None	0.904	N	0.602	0.241	0.455173453901	gnomAD-4.0.0	6.57514E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47054E-05	0	0
E/Q	rs1705290908	None	0.97	N	0.691	0.269	0.370240404367	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/Q	rs1705290908	None	0.97	N	0.691	0.269	0.370240404367	gnomAD-4.0.0	6.57436E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47029E-05	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	0.1273	likely_benign	0.1385	benign	-0.513	Destabilizing	0.014	N	0.468	neutral	N	0.379308781	None	None	N
E/C	0.7983	likely_pathogenic	0.8181	pathogenic	-0.142	Destabilizing	0.998	D	0.789	deleterious	None	None	None	None	N
E/D	0.1998	likely_benign	0.2031	benign	-0.939	Destabilizing	0.904	D	0.602	neutral	N	0.518455451	None	None	N
E/F	0.8231	likely_pathogenic	0.8409	pathogenic	0.046	Stabilizing	0.956	D	0.816	deleterious	None	None	None	None	N
E/G	0.1306	likely_benign	0.1449	benign	-0.869	Destabilizing	0.698	D	0.723	prob.delet.	N	0.484228234	None	None	N
E/H	0.5383	ambiguous	0.5709	pathogenic	-0.136	Destabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	N
E/I	0.5056	ambiguous	0.5236	ambiguous	0.445	Stabilizing	0.915	D	0.781	deleterious	None	None	None	None	N
E/K	0.1798	likely_benign	0.1952	benign	0.077	Stabilizing	0.822	D	0.633	neutral	N	0.480646424	None	None	N
E/L	0.5541	ambiguous	0.5814	pathogenic	0.445	Stabilizing	0.754	D	0.739	prob.delet.	None	None	None	None	N
E/M	0.5618	ambiguous	0.5772	pathogenic	0.742	Stabilizing	0.994	D	0.756	deleterious	None	None	None	None	N
E/N	0.3438	ambiguous	0.3623	ambiguous	-0.57	Destabilizing	0.978	D	0.704	prob.neutral	None	None	None	None	N
E/P	0.9639	likely_pathogenic	0.9686	pathogenic	0.149	Stabilizing	0.978	D	0.745	deleterious	None	None	None	None	N
E/Q	0.1456	likely_benign	0.1553	benign	-0.424	Destabilizing	0.97	D	0.691	prob.neutral	N	0.518455451	None	None	N
E/R	0.3115	likely_benign	0.3407	ambiguous	0.276	Stabilizing	0.978	D	0.704	prob.neutral	None	None	None	None	N
E/S	0.2056	likely_benign	0.2132	benign	-0.792	Destabilizing	0.754	D	0.633	neutral	None	None	None	None	N
E/T	0.2496	likely_benign	0.267	benign	-0.48	Destabilizing	0.86	D	0.729	prob.delet.	None	None	None	None	N
E/V	0.2791	likely_benign	0.2913	benign	0.149	Stabilizing	0.014	N	0.583	neutral	N	0.447093998	None	None	N
E/W	0.9308	likely_pathogenic	0.9426	pathogenic	0.313	Stabilizing	0.998	D	0.767	deleterious	None	None	None	None	N
E/Y	0.7051	likely_pathogenic	0.7257	pathogenic	0.344	Stabilizing	0.978	D	0.769	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.