TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15715	47368;47369;47370	chr2:178618315;178618314;178618313	chr2:179483042;179483041;179483040
N2AB	14074	42445;42446;42447	chr2:178618315;178618314;178618313	chr2:179483042;179483041;179483040
N2A	13147	39664;39665;39666	chr2:178618315;178618314;178618313	chr2:179483042;179483041;179483040
N2B	6650	20173;20174;20175	chr2:178618315;178618314;178618313	chr2:179483042;179483041;179483040
Novex-1	6775	20548;20549;20550	chr2:178618315;178618314;178618313	chr2:179483042;179483041;179483040
Novex-2	6842	20749;20750;20751	chr2:178618315;178618314;178618313	chr2:179483042;179483041;179483040
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: Fn3-1
• Domain position: 59
• Structural Position: 90
• Q(SASA): 0.5956
• 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	rs553017488	-0.459	0.004	D	0.308	0.103	0.304108284078	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
E/D	rs553017488	-0.459	0.004	D	0.308	0.103	0.304108284078	gnomAD-4.0.0	1.77998E-05	None	None	None	None	N	None	2.99312E-05	0	None	0	0	None	0	0	2.24969E-05	0	0
E/K	rs764958886	0.451	0.581	N	0.597	0.301	0.307648195649	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.68E-05	0
E/K	rs764958886	0.451	0.581	N	0.597	0.301	0.307648195649	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	0	6.57E-05	0	0	0	None	0	0	0	0	0
E/K	rs764958886	0.451	0.581	N	0.597	0.301	0.307648195649	gnomAD-4.0.0	2.48057E-06	None	None	None	None	N	None	0	1.6699E-05	None	0	0	None	0	3.29381E-04	8.48077E-07	0	0
E/Q	rs764958886	-0.167	0.83	N	0.706	0.209	0.330331372229	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
E/Q	rs764958886	-0.167	0.83	N	0.706	0.209	0.330331372229	gnomAD-4.0.0	2.0538E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69963E-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
E/A	0.2601	likely_benign	0.2222	benign	-0.755	Destabilizing	0.581	D	0.665	neutral	N	0.467463933	None	None	N
E/C	0.8594	likely_pathogenic	0.802	pathogenic	-0.304	Destabilizing	0.993	D	0.774	deleterious	None	None	None	None	N
E/D	0.2806	likely_benign	0.2623	benign	-0.644	Destabilizing	0.004	N	0.308	neutral	D	0.534808793	None	None	N
E/F	0.8368	likely_pathogenic	0.7687	pathogenic	-0.187	Destabilizing	0.993	D	0.778	deleterious	None	None	None	None	N
E/G	0.351	ambiguous	0.3078	benign	-1.055	Destabilizing	0.83	D	0.711	prob.delet.	N	0.512041043	None	None	N
E/H	0.5588	ambiguous	0.4683	ambiguous	-0.08	Destabilizing	0.98	D	0.739	prob.delet.	None	None	None	None	N
E/I	0.5453	ambiguous	0.4491	ambiguous	0.041	Stabilizing	0.929	D	0.785	deleterious	None	None	None	None	N
E/K	0.3032	likely_benign	0.231	benign	0.043	Stabilizing	0.581	D	0.597	neutral	N	0.477105049	None	None	N
E/L	0.6331	likely_pathogenic	0.5423	ambiguous	0.041	Stabilizing	0.929	D	0.775	deleterious	None	None	None	None	N
E/M	0.6226	likely_pathogenic	0.5437	ambiguous	0.266	Stabilizing	0.993	D	0.785	deleterious	None	None	None	None	N
E/N	0.4117	ambiguous	0.3576	ambiguous	-0.582	Destabilizing	0.764	D	0.747	deleterious	None	None	None	None	N
E/P	0.9621	likely_pathogenic	0.9517	pathogenic	-0.204	Destabilizing	0.929	D	0.799	deleterious	None	None	None	None	N
E/Q	0.1818	likely_benign	0.1529	benign	-0.475	Destabilizing	0.83	D	0.706	prob.neutral	N	0.478093858	None	None	N
E/R	0.3874	ambiguous	0.2936	benign	0.372	Stabilizing	0.866	D	0.751	deleterious	None	None	None	None	N
E/S	0.257	likely_benign	0.2241	benign	-0.78	Destabilizing	0.48	N	0.639	neutral	None	None	None	None	N
E/T	0.2785	likely_benign	0.2335	benign	-0.517	Destabilizing	0.866	D	0.767	deleterious	None	None	None	None	N
E/V	0.3547	ambiguous	0.2926	benign	-0.204	Destabilizing	0.908	D	0.772	deleterious	D	0.541729781	None	None	N
E/W	0.9483	likely_pathogenic	0.9222	pathogenic	0.147	Stabilizing	0.993	D	0.782	deleterious	None	None	None	None	N
E/Y	0.7585	likely_pathogenic	0.6672	pathogenic	0.108	Stabilizing	0.993	D	0.789	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.