TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18436	55531;55532;55533	chr2:178601784;178601783;178601782	chr2:179466511;179466510;179466509
N2AB	16795	50608;50609;50610	chr2:178601784;178601783;178601782	chr2:179466511;179466510;179466509
N2A	15868	47827;47828;47829	chr2:178601784;178601783;178601782	chr2:179466511;179466510;179466509
N2B	9371	28336;28337;28338	chr2:178601784;178601783;178601782	chr2:179466511;179466510;179466509
Novex-1	9496	28711;28712;28713	chr2:178601784;178601783;178601782	chr2:179466511;179466510;179466509
Novex-2	9563	28912;28913;28914	chr2:178601784;178601783;178601782	chr2:179466511;179466510;179466509
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-115
• Domain position: 55
• Structural Position: 125
• Q(SASA): 0.6092
• 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/K	rs201510986	0.837	0.834	N	0.613	0.247	None	gnomAD-2.1.1	3.32E-05	None	None	None	None	N	None	3.74657E-04	0	None	0	0	None	0	None	0	0	0
E/K	rs201510986	0.837	0.834	N	0.613	0.247	None	gnomAD-3.1.2	1.71199E-04	None	None	None	None	N	None	6.04127E-04	6.56E-05	0	0	0	None	0	0	0	0	0
E/K	rs201510986	0.837	0.834	N	0.613	0.247	None	gnomAD-4.0.0	2.49524E-05	None	None	None	None	N	None	4.71609E-04	3.42489E-05	None	0	0	None	0	0	0	0	4.84183E-05

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	0.2156	likely_benign	0.2592	benign	-0.629	Destabilizing	0.834	D	0.679	prob.neutral	N	0.490149781	None	None	N
E/C	0.8411	likely_pathogenic	0.8767	pathogenic	-0.182	Destabilizing	0.998	D	0.707	prob.neutral	None	None	None	None	N
E/D	0.1596	likely_benign	0.1893	benign	-0.484	Destabilizing	0.016	N	0.237	neutral	N	0.503832715	None	None	N
E/F	0.72	likely_pathogenic	0.7486	pathogenic	-0.267	Destabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	N
E/G	0.2878	likely_benign	0.3799	ambiguous	-0.878	Destabilizing	0.946	D	0.677	prob.neutral	N	0.498507574	None	None	N
E/H	0.4219	ambiguous	0.4783	ambiguous	-0.142	Destabilizing	0.998	D	0.659	neutral	None	None	None	None	N
E/I	0.3098	likely_benign	0.3283	benign	0.013	Stabilizing	0.979	D	0.738	prob.delet.	None	None	None	None	N
E/K	0.1971	likely_benign	0.263	benign	0.216	Stabilizing	0.834	D	0.613	neutral	N	0.506120872	None	None	N
E/L	0.3767	ambiguous	0.4083	ambiguous	0.013	Stabilizing	0.979	D	0.746	deleterious	None	None	None	None	N
E/M	0.4445	ambiguous	0.473	ambiguous	0.193	Stabilizing	0.998	D	0.695	prob.neutral	None	None	None	None	N
E/N	0.3045	likely_benign	0.3731	ambiguous	-0.298	Destabilizing	0.921	D	0.703	prob.neutral	None	None	None	None	N
E/P	0.9125	likely_pathogenic	0.9579	pathogenic	-0.181	Destabilizing	0.979	D	0.76	deleterious	None	None	None	None	N
E/Q	0.1302	likely_benign	0.1537	benign	-0.23	Destabilizing	0.946	D	0.637	neutral	D	0.526362858	None	None	N
E/R	0.3276	likely_benign	0.4115	ambiguous	0.453	Stabilizing	0.979	D	0.731	prob.delet.	None	None	None	None	N
E/S	0.2492	likely_benign	0.3011	benign	-0.462	Destabilizing	0.769	D	0.633	neutral	None	None	None	None	N
E/T	0.2275	likely_benign	0.273	benign	-0.247	Destabilizing	0.959	D	0.731	prob.delet.	None	None	None	None	N
E/V	0.1875	likely_benign	0.209	benign	-0.181	Destabilizing	0.973	D	0.743	deleterious	N	0.48613731	None	None	N
E/W	0.8974	likely_pathogenic	0.9177	pathogenic	-0.002	Destabilizing	0.998	D	0.718	prob.delet.	None	None	None	None	N
E/Y	0.624	likely_pathogenic	0.6621	pathogenic	0.007	Stabilizing	0.998	D	0.708	prob.delet.	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.