TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17440	52543;52544;52545	chr2:178608693;178608692;178608691	chr2:179473420;179473419;179473418
N2AB	15799	47620;47621;47622	chr2:178608693;178608692;178608691	chr2:179473420;179473419;179473418
N2A	14872	44839;44840;44841	chr2:178608693;178608692;178608691	chr2:179473420;179473419;179473418
N2B	8375	25348;25349;25350	chr2:178608693;178608692;178608691	chr2:179473420;179473419;179473418
Novex-1	8500	25723;25724;25725	chr2:178608693;178608692;178608691	chr2:179473420;179473419;179473418
Novex-2	8567	25924;25925;25926	chr2:178608693;178608692;178608691	chr2:179473420;179473419;179473418
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: Fn3-14
• Domain position: 72
• Structural Position: 103
• Q(SASA): 0.3861
• 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/G	rs2055527887	None	1.0	N	0.753	0.563	0.471052466308	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.95236E-04	None	0	0	0	0	0
E/G	rs2055527887	None	1.0	N	0.753	0.563	0.471052466308	gnomAD-4.0.0	2.5668E-06	None	None	None	None	N	None	0	0	None	0	2.44427E-05	None	0	0	0	0	2.85095E-05
E/K	None	None	0.999	N	0.61	0.394	0.383921772103	gnomAD-4.0.0	1.59447E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43419E-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	0.2645	likely_benign	0.2459	benign	-0.973	Destabilizing	0.999	D	0.701	prob.neutral	N	0.484588422	None	None	N
E/C	0.89	likely_pathogenic	0.8932	pathogenic	-0.517	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/D	0.2506	likely_benign	0.2959	benign	-1.333	Destabilizing	0.999	D	0.493	neutral	N	0.478814751	None	None	N
E/F	0.9031	likely_pathogenic	0.9074	pathogenic	-0.322	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
E/G	0.4522	ambiguous	0.4261	ambiguous	-1.41	Destabilizing	1.0	D	0.753	deleterious	N	0.493084345	None	None	N
E/H	0.7059	likely_pathogenic	0.6922	pathogenic	-0.634	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
E/I	0.4583	ambiguous	0.4598	ambiguous	0.252	Stabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/K	0.4163	ambiguous	0.3866	ambiguous	-0.888	Destabilizing	0.999	D	0.61	neutral	N	0.469722943	None	None	N
E/L	0.6146	likely_pathogenic	0.6065	pathogenic	0.252	Stabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/M	0.619	likely_pathogenic	0.589	pathogenic	0.866	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/N	0.4321	ambiguous	0.4632	ambiguous	-1.399	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
E/P	0.6865	likely_pathogenic	0.7347	pathogenic	-0.136	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/Q	0.2325	likely_benign	0.2086	benign	-1.174	Destabilizing	1.0	D	0.627	neutral	N	0.471724406	None	None	N
E/R	0.5495	ambiguous	0.5272	ambiguous	-0.675	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
E/S	0.3489	ambiguous	0.3464	ambiguous	-1.872	Destabilizing	0.999	D	0.656	neutral	None	None	None	None	N
E/T	0.314	likely_benign	0.3061	benign	-1.487	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/V	0.2859	likely_benign	0.2781	benign	-0.136	Destabilizing	1.0	D	0.789	deleterious	N	0.480335688	None	None	N
E/W	0.9582	likely_pathogenic	0.9581	pathogenic	-0.128	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/Y	0.8023	likely_pathogenic	0.8109	pathogenic	-0.06	Destabilizing	1.0	D	0.771	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.