TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26900	80923;80924;80925	chr2:178565434;178565433;178565432	chr2:179430161;179430160;179430159
N2AB	25259	76000;76001;76002	chr2:178565434;178565433;178565432	chr2:179430161;179430160;179430159
N2A	24332	73219;73220;73221	chr2:178565434;178565433;178565432	chr2:179430161;179430160;179430159
N2B	17835	53728;53729;53730	chr2:178565434;178565433;178565432	chr2:179430161;179430160;179430159
Novex-1	17960	54103;54104;54105	chr2:178565434;178565433;178565432	chr2:179430161;179430160;179430159
Novex-2	18027	54304;54305;54306	chr2:178565434;178565433;178565432	chr2:179430161;179430160;179430159
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: 21
• Structural Position: 31
• Q(SASA): 0.4723
• Predicted PPI site: I

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	rs751557221	-0.694	0.02	N	0.225	0.172	0.321393169273	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
E/D	rs751557221	-0.694	0.02	N	0.225	0.172	0.321393169273	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	1.93573E-04	None	0	0	0	0	0
E/D	rs751557221	-0.694	0.02	N	0.225	0.172	0.321393169273	gnomAD-4.0.0	2.56345E-06	None	None	None	None	I	None	0	0	None	0	2.42789E-05	None	0	0	0	0	2.84657E-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	0.2192	likely_benign	0.2373	benign	-0.783	Destabilizing	0.939	D	0.565	neutral	N	0.504850676	None	None	I
E/C	0.8714	likely_pathogenic	0.8848	pathogenic	-0.413	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	I
E/D	0.1496	likely_benign	0.1346	benign	-0.906	Destabilizing	0.02	N	0.225	neutral	N	0.481516003	None	None	I
E/F	0.8464	likely_pathogenic	0.8512	pathogenic	-0.237	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	I
E/G	0.3092	likely_benign	0.3306	benign	-1.113	Destabilizing	0.939	D	0.599	neutral	N	0.513777899	None	None	I
E/H	0.5293	ambiguous	0.5497	ambiguous	-0.356	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	I
E/I	0.4241	ambiguous	0.4329	ambiguous	0.107	Stabilizing	0.993	D	0.781	deleterious	None	None	None	None	I
E/K	0.2692	likely_benign	0.2903	benign	-0.352	Destabilizing	0.939	D	0.467	neutral	N	0.51126012	None	None	I
E/L	0.5475	ambiguous	0.5522	ambiguous	0.107	Stabilizing	0.993	D	0.766	deleterious	None	None	None	None	I
E/M	0.5596	ambiguous	0.562	ambiguous	0.423	Stabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	I
E/N	0.2877	likely_benign	0.2858	benign	-0.9	Destabilizing	0.973	D	0.591	neutral	None	None	None	None	I
E/P	0.8213	likely_pathogenic	0.8315	pathogenic	-0.168	Destabilizing	0.993	D	0.749	deleterious	None	None	None	None	I
E/Q	0.1768	likely_benign	0.1939	benign	-0.778	Destabilizing	0.991	D	0.56	neutral	N	0.517532731	None	None	I
E/R	0.3999	ambiguous	0.4382	ambiguous	-0.05	Destabilizing	0.993	D	0.646	neutral	None	None	None	None	I
E/S	0.2374	likely_benign	0.2495	benign	-1.132	Destabilizing	0.953	D	0.471	neutral	None	None	None	None	I
E/T	0.2357	likely_benign	0.254	benign	-0.855	Destabilizing	0.993	D	0.695	prob.neutral	None	None	None	None	I
E/V	0.2492	likely_benign	0.2593	benign	-0.168	Destabilizing	0.991	D	0.747	deleterious	D	0.537678717	None	None	I
E/W	0.9496	likely_pathogenic	0.9498	pathogenic	0.04	Stabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	I
E/Y	0.7577	likely_pathogenic	0.7651	pathogenic	0.02	Stabilizing	0.999	D	0.742	deleterious	None	None	None	None	I

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.