TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8164	24715;24716;24717	chr2:178718710;178718709;178718708	chr2:179583437;179583436;179583435
N2AB	7847	23764;23765;23766	chr2:178718710;178718709;178718708	chr2:179583437;179583436;179583435
N2A	6920	20983;20984;20985	chr2:178718710;178718709;178718708	chr2:179583437;179583436;179583435
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: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-66
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.2263
• 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
H/D	rs367916657	-0.678	0.002	N	0.181	0.324	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
H/D	rs367916657	-0.678	0.002	N	0.181	0.324	None	gnomAD-4.0.0	2.73731E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59842E-06	0	0
H/Q	None	None	0.023	N	0.181	0.219	0.104622674875	gnomAD-4.0.0	6.84376E-06	None	None	None	None	N	None	5.97764E-05	0	None	0	0	None	0	0	7.19722E-06	0	0
H/Y	None	None	0.917	D	0.465	0.278	0.487277728379	gnomAD-4.0.0	1.36866E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79921E-06	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
H/A	0.2517	likely_benign	0.2638	benign	-0.309	Destabilizing	0.176	N	0.335	neutral	None	None	None	None	N
H/C	0.1942	likely_benign	0.2099	benign	0.209	Stabilizing	0.995	D	0.563	neutral	None	None	None	None	N
H/D	0.2295	likely_benign	0.246	benign	0.186	Stabilizing	0.002	N	0.181	neutral	N	0.510238613	None	None	N
H/E	0.25	likely_benign	0.2608	benign	0.212	Stabilizing	0.176	N	0.251	neutral	None	None	None	None	N
H/F	0.3439	ambiguous	0.3546	ambiguous	0.146	Stabilizing	0.981	D	0.593	neutral	None	None	None	None	N
H/G	0.3035	likely_benign	0.3254	benign	-0.585	Destabilizing	0.495	N	0.387	neutral	None	None	None	None	N
H/I	0.3245	likely_benign	0.3333	benign	0.398	Stabilizing	0.704	D	0.624	neutral	None	None	None	None	N
H/K	0.1866	likely_benign	0.1955	benign	-0.181	Destabilizing	0.329	N	0.436	neutral	None	None	None	None	N
H/L	0.1344	likely_benign	0.1405	benign	0.398	Stabilizing	0.425	N	0.5	neutral	N	0.505659512	None	None	N
H/M	0.4569	ambiguous	0.4727	ambiguous	0.347	Stabilizing	0.944	D	0.569	neutral	None	None	None	None	N
H/N	0.1052	likely_benign	0.1044	benign	-0.011	Destabilizing	0.01	N	0.158	neutral	N	0.44597649	None	None	N
H/P	0.2497	likely_benign	0.2771	benign	0.187	Stabilizing	0.784	D	0.576	neutral	N	0.483312926	None	None	N
H/Q	0.1315	likely_benign	0.1352	benign	0.042	Stabilizing	0.023	N	0.181	neutral	N	0.473451093	None	None	N
H/R	0.0704	likely_benign	0.0727	benign	-0.453	Destabilizing	0.473	N	0.421	neutral	N	0.461407303	None	None	N
H/S	0.1892	likely_benign	0.198	benign	-0.19	Destabilizing	0.037	N	0.18	neutral	None	None	None	None	N
H/T	0.2136	likely_benign	0.2207	benign	-0.066	Destabilizing	0.013	N	0.284	neutral	None	None	None	None	N
H/V	0.248	likely_benign	0.2512	benign	0.187	Stabilizing	0.704	D	0.545	neutral	None	None	None	None	N
H/W	0.3973	ambiguous	0.4177	ambiguous	0.247	Stabilizing	0.995	D	0.569	neutral	None	None	None	None	N
H/Y	0.1081	likely_benign	0.1083	benign	0.587	Stabilizing	0.917	D	0.465	neutral	D	0.532211395	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.