TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9003	27232;27233;27234	chr2:178713127;178713126;178713125	chr2:179577854;179577853;179577852
N2AB	8686	26281;26282;26283	chr2:178713127;178713126;178713125	chr2:179577854;179577853;179577852
N2A	7759	23500;23501;23502	chr2:178713127;178713126;178713125	chr2:179577854;179577853;179577852
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-75
• Domain position: 78
• Structural Position: 162
• Q(SASA): 1.0092
• 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
M/I	None	None	None	N	0.181	0.137	0.15556083564	gnomAD-4.0.0	1.3685E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.31916E-05	0
M/T	rs2076906083	None	None	N	0.183	0.098	0.393775345888	gnomAD-4.0.0	4.78977E-06	None	None	None	None	I	None	8.96325E-05	0	None	0	2.52016E-05	None	0	0	1.79901E-06	1.15955E-05	0
M/V	None	None	None	N	0.173	0.074	0.165133752707	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	6.17284E-04	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
M/A	0.114	likely_benign	0.1115	benign	-0.16	Destabilizing	None	N	0.177	neutral	None	None	None	None	I
M/C	0.633	likely_pathogenic	0.5758	pathogenic	-0.362	Destabilizing	0.041	N	0.359	neutral	None	None	None	None	I
M/D	0.3469	ambiguous	0.3448	ambiguous	0.329	Stabilizing	None	N	0.239	neutral	None	None	None	None	I
M/E	0.159	likely_benign	0.17	benign	0.259	Stabilizing	None	N	0.201	neutral	None	None	None	None	I
M/F	0.1864	likely_benign	0.2162	benign	-0.231	Destabilizing	0.009	N	0.266	neutral	None	None	None	None	I
M/G	0.2473	likely_benign	0.2587	benign	-0.229	Destabilizing	None	N	0.259	neutral	None	None	None	None	I
M/H	0.2716	likely_benign	0.2586	benign	0.362	Stabilizing	0.116	N	0.403	neutral	None	None	None	None	I
M/I	0.0947	likely_benign	0.1098	benign	-0.079	Destabilizing	None	N	0.181	neutral	N	0.413712143	None	None	I
M/K	0.0845	likely_benign	0.0916	benign	0.426	Stabilizing	None	N	0.185	neutral	N	0.362781891	None	None	I
M/L	0.0927	likely_benign	0.0975	benign	-0.079	Destabilizing	None	N	0.266	neutral	N	0.397203895	None	None	I
M/N	0.1843	likely_benign	0.1913	benign	0.565	Stabilizing	0.002	N	0.325	neutral	None	None	None	None	I
M/P	0.3345	likely_benign	0.3544	ambiguous	-0.085	Destabilizing	0.008	N	0.325	neutral	None	None	None	None	I
M/Q	0.1256	likely_benign	0.1275	benign	0.405	Stabilizing	0.004	N	0.263	neutral	None	None	None	None	I
M/R	0.0807	likely_benign	0.0911	benign	0.828	Stabilizing	0.001	N	0.315	neutral	N	0.396145103	None	None	I
M/S	0.1421	likely_benign	0.1393	benign	0.182	Stabilizing	None	N	0.179	neutral	None	None	None	None	I
M/T	0.0736	likely_benign	0.0723	benign	0.194	Stabilizing	None	N	0.183	neutral	N	0.390296566	None	None	I
M/V	0.0459	likely_benign	0.0498	benign	-0.085	Destabilizing	None	N	0.173	neutral	N	0.416405732	None	None	I
M/W	0.4674	ambiguous	0.4899	ambiguous	-0.254	Destabilizing	0.316	N	0.304	neutral	None	None	None	None	I
M/Y	0.377	ambiguous	0.3853	ambiguous	-0.041	Destabilizing	0.018	N	0.351	neutral	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.