TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35434	106525;106526;106527	chr2:178530315;178530314;178530313	chr2:179395042;179395041;179395040
N2AB	33793	101602;101603;101604	chr2:178530315;178530314;178530313	chr2:179395042;179395041;179395040
N2A	32866	98821;98822;98823	chr2:178530315;178530314;178530313	chr2:179395042;179395041;179395040
N2B	26369	79330;79331;79332	chr2:178530315;178530314;178530313	chr2:179395042;179395041;179395040
Novex-1	26494	79705;79706;79707	chr2:178530315;178530314;178530313	chr2:179395042;179395041;179395040
Novex-2	26561	79906;79907;79908	chr2:178530315;178530314;178530313	chr2:179395042;179395041;179395040
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-166
• Domain position: 15
• Structural Position: 24
• Q(SASA): 0.58
• 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
D/E	rs1371891927	0.204	None	N	0.193	0.086	0.0551355673512	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	1.14758E-04	0	None	0	0	None	0	None	0	0	0
D/E	rs1371891927	0.204	None	N	0.193	0.086	0.0551355673512	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
D/E	rs1371891927	0.204	None	N	0.193	0.086	0.0551355673512	gnomAD-4.0.0	6.5703E-06	None	None	None	None	N	None	2.41289E-05	0	None	0	0	None	0	0	0	0	0
D/G	rs1362199779	0.066	0.037	N	0.473	0.105	0.0716867268079	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.85E-06	0
D/G	rs1362199779	0.066	0.037	N	0.473	0.105	0.0716867268079	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
D/G	rs1362199779	0.066	0.037	N	0.473	0.105	0.0716867268079	gnomAD-4.0.0	3.71785E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.08533E-06	0	0
D/H	rs770168784	0.016	0.395	N	0.591	0.173	0.226586394389	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.85E-06	0
D/H	rs770168784	0.016	0.395	N	0.591	0.173	0.226586394389	gnomAD-4.0.0	6.84185E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99431E-07	0	0
D/Y	None	None	0.801	D	0.614	0.408	0.611906392123	gnomAD-4.0.0	6.84185E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99431E-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
D/A	0.161	likely_benign	0.1951	benign	-0.077	Destabilizing	0.157	N	0.499	neutral	N	0.478032981	None	None	N
D/C	0.6475	likely_pathogenic	0.6859	pathogenic	0.4	Stabilizing	0.953	D	0.62	neutral	None	None	None	None	N
D/E	0.1879	likely_benign	0.2112	benign	-0.088	Destabilizing	None	N	0.193	neutral	N	0.480590496	None	None	N
D/F	0.5291	ambiguous	0.6006	pathogenic	-0.336	Destabilizing	0.842	D	0.617	neutral	None	None	None	None	N
D/G	0.121	likely_benign	0.133	benign	-0.184	Destabilizing	0.037	N	0.473	neutral	N	0.328052376	None	None	N
D/H	0.259	likely_benign	0.3122	benign	-0.176	Destabilizing	0.395	N	0.591	neutral	N	0.492116999	None	None	N
D/I	0.3688	ambiguous	0.451	ambiguous	0.139	Stabilizing	0.637	D	0.613	neutral	None	None	None	None	N
D/K	0.3042	likely_benign	0.342	ambiguous	0.7	Stabilizing	0.11	N	0.478	neutral	None	None	None	None	N
D/L	0.355	ambiguous	0.4205	ambiguous	0.139	Stabilizing	0.198	N	0.621	neutral	None	None	None	None	N
D/M	0.6249	likely_pathogenic	0.6953	pathogenic	0.331	Stabilizing	0.953	D	0.612	neutral	None	None	None	None	N
D/N	0.0807	likely_benign	0.0899	benign	0.573	Stabilizing	None	N	0.186	neutral	N	0.423910494	None	None	N
D/P	0.6202	likely_pathogenic	0.7068	pathogenic	0.086	Stabilizing	0.637	D	0.571	neutral	None	None	None	None	N
D/Q	0.316	likely_benign	0.3709	ambiguous	0.565	Stabilizing	0.11	N	0.403	neutral	None	None	None	None	N
D/R	0.3325	likely_benign	0.3851	ambiguous	0.618	Stabilizing	0.198	N	0.587	neutral	None	None	None	None	N
D/S	0.1039	likely_benign	0.1219	benign	0.497	Stabilizing	0.049	N	0.362	neutral	None	None	None	None	N
D/T	0.222	likely_benign	0.261	benign	0.584	Stabilizing	0.198	N	0.515	neutral	None	None	None	None	N
D/V	0.2357	likely_benign	0.2883	benign	0.086	Stabilizing	0.57	D	0.623	neutral	D	0.532520826	None	None	N
D/W	0.8613	likely_pathogenic	0.893	pathogenic	-0.327	Destabilizing	0.953	D	0.633	neutral	None	None	None	None	N
D/Y	0.221	likely_benign	0.2498	benign	-0.125	Destabilizing	0.801	D	0.614	neutral	D	0.532694185	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.