TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28896	86911;86912;86913	chr2:178559446;178559445;178559444	chr2:179424173;179424172;179424171
N2AB	27255	81988;81989;81990	chr2:178559446;178559445;178559444	chr2:179424173;179424172;179424171
N2A	26328	79207;79208;79209	chr2:178559446;178559445;178559444	chr2:179424173;179424172;179424171
N2B	19831	59716;59717;59718	chr2:178559446;178559445;178559444	chr2:179424173;179424172;179424171
Novex-1	19956	60091;60092;60093	chr2:178559446;178559445;178559444	chr2:179424173;179424172;179424171
Novex-2	20023	60292;60293;60294	chr2:178559446;178559445;178559444	chr2:179424173;179424172;179424171
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-98
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.1329
• 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
T/I	None	None	0.999	N	0.754	0.397	0.546000776237	gnomAD-4.0.0	1.59144E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85874E-06	0	0
T/P	rs778149999	-0.756	0.999	N	0.752	0.434	0.494838880905	gnomAD-2.1.1	1.2E-05	None	None	None	None	N	None	0	8.69E-05	None	0	0	None	0	None	0	0	0
T/P	rs778149999	-0.756	0.999	N	0.752	0.434	0.494838880905	gnomAD-4.0.0	6.3658E-06	None	None	None	None	N	None	0	9.14578E-05	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
T/A	0.1283	likely_benign	0.1243	benign	-1.024	Destabilizing	0.962	D	0.497	neutral	N	0.46249502	None	None	N
T/C	0.5132	ambiguous	0.5115	ambiguous	-0.538	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
T/D	0.7123	likely_pathogenic	0.674	pathogenic	-0.924	Destabilizing	0.998	D	0.683	prob.neutral	None	None	None	None	N
T/E	0.7306	likely_pathogenic	0.6827	pathogenic	-0.849	Destabilizing	0.998	D	0.673	neutral	None	None	None	None	N
T/F	0.6223	likely_pathogenic	0.6082	pathogenic	-0.902	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
T/G	0.3751	ambiguous	0.3542	ambiguous	-1.37	Destabilizing	0.994	D	0.606	neutral	None	None	None	None	N
T/H	0.6012	likely_pathogenic	0.567	pathogenic	-1.681	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
T/I	0.4719	ambiguous	0.4734	ambiguous	-0.164	Destabilizing	0.999	D	0.754	deleterious	N	0.49833839	None	None	N
T/K	0.6809	likely_pathogenic	0.6211	pathogenic	-0.931	Destabilizing	0.998	D	0.68	prob.neutral	None	None	None	None	N
T/L	0.2692	likely_benign	0.2571	benign	-0.164	Destabilizing	0.997	D	0.592	neutral	None	None	None	None	N
T/M	0.1634	likely_benign	0.1614	benign	0.206	Stabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
T/N	0.2637	likely_benign	0.2492	benign	-1.139	Destabilizing	0.998	D	0.686	prob.neutral	N	0.447946855	None	None	N
T/P	0.8236	likely_pathogenic	0.7725	pathogenic	-0.417	Destabilizing	0.999	D	0.752	deleterious	N	0.508363383	None	None	N
T/Q	0.5317	ambiguous	0.4903	ambiguous	-1.134	Destabilizing	0.999	D	0.756	deleterious	None	None	None	None	N
T/R	0.6342	likely_pathogenic	0.5603	ambiguous	-0.852	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
T/S	0.1335	likely_benign	0.1286	benign	-1.344	Destabilizing	0.825	D	0.327	neutral	N	0.422357764	None	None	N
T/V	0.3209	likely_benign	0.3275	benign	-0.417	Destabilizing	0.997	D	0.567	neutral	None	None	None	None	N
T/W	0.894	likely_pathogenic	0.8787	pathogenic	-0.943	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
T/Y	0.7211	likely_pathogenic	0.6922	pathogenic	-0.686	Destabilizing	1.0	D	0.764	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.