TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27150	81673;81674;81675	chr2:178564684;178564683;178564682	chr2:179429411;179429410;179429409
N2AB	25509	76750;76751;76752	chr2:178564684;178564683;178564682	chr2:179429411;179429410;179429409
N2A	24582	73969;73970;73971	chr2:178564684;178564683;178564682	chr2:179429411;179429410;179429409
N2B	18085	54478;54479;54480	chr2:178564684;178564683;178564682	chr2:179429411;179429410;179429409
Novex-1	18210	54853;54854;54855	chr2:178564684;178564683;178564682	chr2:179429411;179429410;179429409
Novex-2	18277	55054;55055;55056	chr2:178564684;178564683;178564682	chr2:179429411;179429410;179429409
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: Fn3-85
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.2881
• 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/K	rs1466718214	-0.979	0.999	N	0.55	0.406	0.378498632473	gnomAD-2.1.1	8.06E-06	None	None	None	None	I	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
E/K	rs1466718214	-0.979	0.999	N	0.55	0.406	0.378498632473	gnomAD-4.0.0	3.18416E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.8659E-05	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	0.5096	ambiguous	0.4628	ambiguous	-1.44	Destabilizing	0.999	D	0.677	prob.neutral	N	0.469505453	None	None	I
E/C	0.9228	likely_pathogenic	0.9056	pathogenic	-1.047	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	I
E/D	0.9152	likely_pathogenic	0.8834	pathogenic	-1.581	Destabilizing	0.999	D	0.485	neutral	N	0.520744025	None	None	I
E/F	0.9614	likely_pathogenic	0.9456	pathogenic	-1.39	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	I
E/G	0.7802	likely_pathogenic	0.738	pathogenic	-1.809	Destabilizing	1.0	D	0.765	deleterious	N	0.498031415	None	None	I
E/H	0.9161	likely_pathogenic	0.8884	pathogenic	-1.568	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
E/I	0.5065	ambiguous	0.4517	ambiguous	-0.405	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	I
E/K	0.4883	ambiguous	0.4395	ambiguous	-1.588	Destabilizing	0.999	D	0.55	neutral	N	0.466733976	None	None	I
E/L	0.7594	likely_pathogenic	0.7078	pathogenic	-0.405	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	I
E/M	0.6401	likely_pathogenic	0.5674	pathogenic	0.241	Stabilizing	1.0	D	0.834	deleterious	None	None	None	None	I
E/N	0.9052	likely_pathogenic	0.8656	pathogenic	-1.762	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
E/P	0.9989	likely_pathogenic	0.9987	pathogenic	-0.733	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
E/Q	0.2147	likely_benign	0.1976	benign	-1.538	Destabilizing	1.0	D	0.633	neutral	N	0.473379793	None	None	I
E/R	0.653	likely_pathogenic	0.6227	pathogenic	-1.451	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
E/S	0.7129	likely_pathogenic	0.637	pathogenic	-2.358	Highly Destabilizing	0.999	D	0.589	neutral	None	None	None	None	I
E/T	0.6723	likely_pathogenic	0.5903	pathogenic	-2.023	Highly Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
E/V	0.3165	likely_benign	0.278	benign	-0.733	Destabilizing	1.0	D	0.817	deleterious	N	0.450189366	None	None	I
E/W	0.9907	likely_pathogenic	0.9866	pathogenic	-1.467	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
E/Y	0.9561	likely_pathogenic	0.9391	pathogenic	-1.23	Destabilizing	1.0	D	0.847	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.