TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19581	58966;58967;58968	chr2:178593467;178593466;178593465	chr2:179458194;179458193;179458192
N2AB	17940	54043;54044;54045	chr2:178593467;178593466;178593465	chr2:179458194;179458193;179458192
N2A	17013	51262;51263;51264	chr2:178593467;178593466;178593465	chr2:179458194;179458193;179458192
N2B	10516	31771;31772;31773	chr2:178593467;178593466;178593465	chr2:179458194;179458193;179458192
Novex-1	10641	32146;32147;32148	chr2:178593467;178593466;178593465	chr2:179458194;179458193;179458192
Novex-2	10708	32347;32348;32349	chr2:178593467;178593466;178593465	chr2:179458194;179458193;179458192
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-30
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.4411
• 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
D/E	None	None	0.003	N	0.401	0.103	0.273503213844	gnomAD-4.0.0	1.37237E-06	None	None	None	None	N	None	0	0	None	0	2.53203E-05	None	0	0	9.00169E-07	0	0
D/N	None	None	0.782	N	0.585	0.251	0.388653054685	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	0
D/V	rs1421309086	None	0.642	N	0.744	0.27	0.391470661076	gnomAD-4.0.0	1.60233E-06	None	None	None	None	N	None	5.77768E-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
D/A	0.1522	likely_benign	0.1043	benign	-0.307	Destabilizing	0.003	N	0.58	neutral	N	0.506723013	None	None	N
D/C	0.6216	likely_pathogenic	0.5437	ambiguous	-0.193	Destabilizing	0.973	D	0.772	deleterious	None	None	None	None	N
D/E	0.2112	likely_benign	0.1693	benign	-0.719	Destabilizing	0.003	N	0.401	neutral	N	0.485019589	None	None	N
D/F	0.7021	likely_pathogenic	0.5877	pathogenic	-0.299	Destabilizing	0.704	D	0.757	deleterious	None	None	None	None	N
D/G	0.1364	likely_benign	0.1122	benign	-0.604	Destabilizing	0.338	N	0.608	neutral	N	0.464372171	None	None	N
D/H	0.3636	ambiguous	0.2877	benign	-0.795	Destabilizing	0.782	D	0.661	neutral	N	0.511563313	None	None	N
D/I	0.5933	likely_pathogenic	0.4664	ambiguous	0.458	Stabilizing	0.826	D	0.751	deleterious	None	None	None	None	N
D/K	0.4943	ambiguous	0.4002	ambiguous	-0.703	Destabilizing	0.404	N	0.666	neutral	None	None	None	None	N
D/L	0.4587	ambiguous	0.3443	ambiguous	0.458	Stabilizing	0.704	D	0.743	deleterious	None	None	None	None	N
D/M	0.6804	likely_pathogenic	0.5711	pathogenic	0.822	Stabilizing	0.973	D	0.775	deleterious	None	None	None	None	N
D/N	0.1396	likely_benign	0.1103	benign	-0.786	Destabilizing	0.782	D	0.585	neutral	N	0.48354433	None	None	N
D/P	0.8594	likely_pathogenic	0.7953	pathogenic	0.228	Stabilizing	0.906	D	0.627	neutral	None	None	None	None	N
D/Q	0.4158	ambiguous	0.3385	benign	-0.666	Destabilizing	0.704	D	0.554	neutral	None	None	None	None	N
D/R	0.5501	ambiguous	0.4483	ambiguous	-0.626	Destabilizing	0.826	D	0.716	prob.delet.	None	None	None	None	N
D/S	0.1159	likely_benign	0.0912	benign	-1.016	Destabilizing	0.404	N	0.551	neutral	None	None	None	None	N
D/T	0.2976	likely_benign	0.2296	benign	-0.8	Destabilizing	0.575	D	0.665	neutral	None	None	None	None	N
D/V	0.3594	ambiguous	0.2673	benign	0.228	Stabilizing	0.642	D	0.744	deleterious	N	0.500967476	None	None	N
D/W	0.9176	likely_pathogenic	0.8858	pathogenic	-0.337	Destabilizing	0.973	D	0.783	deleterious	None	None	None	None	N
D/Y	0.3048	likely_benign	0.244	benign	-0.165	Destabilizing	0.007	N	0.671	neutral	N	0.493966037	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.