TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28124	84595;84596;84597	chr2:178561762;178561761;178561760	chr2:179426489;179426488;179426487
N2AB	26483	79672;79673;79674	chr2:178561762;178561761;178561760	chr2:179426489;179426488;179426487
N2A	25556	76891;76892;76893	chr2:178561762;178561761;178561760	chr2:179426489;179426488;179426487
N2B	19059	57400;57401;57402	chr2:178561762;178561761;178561760	chr2:179426489;179426488;179426487
Novex-1	19184	57775;57776;57777	chr2:178561762;178561761;178561760	chr2:179426489;179426488;179426487
Novex-2	19251	57976;57977;57978	chr2:178561762;178561761;178561760	chr2:179426489;179426488;179426487
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: Fn3-92
• Domain position: 70
• Structural Position: 103
• Q(SASA): 0.361
• 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	rs1295072546	-0.308	0.999	N	0.621	0.381	0.36453787251	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
E/K	rs1295072546	-0.308	0.999	N	0.621	0.381	0.36453787251	gnomAD-4.0.0	1.36864E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.87357E-05	0	8.99536E-07	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	0.2248	likely_benign	0.2205	benign	-1.115	Destabilizing	0.999	D	0.714	prob.delet.	N	0.488703025	None	None	N
E/C	0.9011	likely_pathogenic	0.8897	pathogenic	-0.462	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
E/D	0.4967	ambiguous	0.5048	ambiguous	-0.941	Destabilizing	0.999	D	0.476	neutral	N	0.493298155	None	None	N
E/F	0.9065	likely_pathogenic	0.8893	pathogenic	-0.571	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/G	0.4026	ambiguous	0.3916	ambiguous	-1.471	Destabilizing	1.0	D	0.763	deleterious	N	0.49966771	None	None	N
E/H	0.6981	likely_pathogenic	0.675	pathogenic	-0.786	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	N
E/I	0.5175	ambiguous	0.4787	ambiguous	-0.137	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/K	0.2341	likely_benign	0.2125	benign	-0.483	Destabilizing	0.999	D	0.621	neutral	N	0.483712595	None	None	N
E/L	0.5835	likely_pathogenic	0.5638	ambiguous	-0.137	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
E/M	0.5825	likely_pathogenic	0.5644	pathogenic	0.378	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
E/N	0.5618	ambiguous	0.5289	ambiguous	-0.966	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
E/P	0.7394	likely_pathogenic	0.7182	pathogenic	-0.443	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/Q	0.1638	likely_benign	0.1505	benign	-0.857	Destabilizing	1.0	D	0.622	neutral	N	0.468597308	None	None	N
E/R	0.3823	ambiguous	0.3398	benign	-0.244	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
E/S	0.3381	likely_benign	0.3393	benign	-1.322	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
E/T	0.3503	ambiguous	0.3329	benign	-1.015	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/V	0.318	likely_benign	0.2914	benign	-0.443	Destabilizing	1.0	D	0.797	deleterious	N	0.485273212	None	None	N
E/W	0.9732	likely_pathogenic	0.9698	pathogenic	-0.246	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/Y	0.8494	likely_pathogenic	0.8305	pathogenic	-0.281	Destabilizing	1.0	D	0.776	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.