TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19332	58219;58220;58221	chr2:178594500;178594499;178594498	chr2:179459227;179459226;179459225
N2AB	17691	53296;53297;53298	chr2:178594500;178594499;178594498	chr2:179459227;179459226;179459225
N2A	16764	50515;50516;50517	chr2:178594500;178594499;178594498	chr2:179459227;179459226;179459225
N2B	10267	31024;31025;31026	chr2:178594500;178594499;178594498	chr2:179459227;179459226;179459225
Novex-1	10392	31399;31400;31401	chr2:178594500;178594499;178594498	chr2:179459227;179459226;179459225
Novex-2	10459	31600;31601;31602	chr2:178594500;178594499;178594498	chr2:179459227;179459226;179459225
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Fn3-28
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.4518
• 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/Q	rs762362185	-0.235	0.642	N	0.381	0.152	0.190952846119	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
H/Q	rs762362185	-0.235	0.642	N	0.381	0.152	0.190952846119	gnomAD-4.0.0	6.57661E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47085E-05	0	0
H/Y	rs770403940	1.125	0.002	N	0.148	0.137	0.17948927462	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
H/Y	rs770403940	1.125	0.002	N	0.148	0.137	0.17948927462	gnomAD-4.0.0	1.59214E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85995E-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	0.2016	likely_benign	0.2	benign	-0.103	Destabilizing	0.329	N	0.321	neutral	None	None	None	None	N
H/C	0.142	likely_benign	0.1325	benign	0.431	Stabilizing	0.995	D	0.458	neutral	None	None	None	None	N
H/D	0.2347	likely_benign	0.1981	benign	-0.149	Destabilizing	0.642	D	0.393	neutral	N	0.448773574	None	None	N
H/E	0.1904	likely_benign	0.1707	benign	-0.097	Destabilizing	0.495	N	0.293	neutral	None	None	None	None	N
H/F	0.2434	likely_benign	0.2535	benign	0.825	Stabilizing	0.007	N	0.255	neutral	None	None	None	None	N
H/G	0.287	likely_benign	0.2681	benign	-0.416	Destabilizing	0.329	N	0.367	neutral	None	None	None	None	N
H/I	0.173	likely_benign	0.1793	benign	0.721	Stabilizing	0.704	D	0.507	neutral	None	None	None	None	N
H/K	0.152	likely_benign	0.1423	benign	-0.123	Destabilizing	0.329	N	0.353	neutral	None	None	None	None	N
H/L	0.1034	likely_benign	0.1029	benign	0.721	Stabilizing	0.27	N	0.374	neutral	N	0.414044925	None	None	N
H/M	0.2801	likely_benign	0.3017	benign	0.483	Stabilizing	0.981	D	0.474	neutral	None	None	None	None	N
H/N	0.0885	likely_benign	0.0856	benign	-0.194	Destabilizing	0.642	D	0.299	neutral	N	0.460142574	None	None	N
H/P	0.6309	likely_pathogenic	0.5667	pathogenic	0.471	Stabilizing	0.927	D	0.561	neutral	N	0.512419621	None	None	N
H/Q	0.0982	likely_benign	0.0929	benign	-0.037	Destabilizing	0.642	D	0.381	neutral	N	0.414178211	None	None	N
H/R	0.0862	likely_benign	0.0789	benign	-0.677	Destabilizing	0.002	N	0.209	neutral	N	0.424280562	None	None	N
H/S	0.1517	likely_benign	0.1454	benign	-0.14	Destabilizing	0.031	N	0.244	neutral	None	None	None	None	N
H/T	0.1292	likely_benign	0.1276	benign	0.015	Stabilizing	0.543	D	0.408	neutral	None	None	None	None	N
H/V	0.1324	likely_benign	0.1384	benign	0.471	Stabilizing	0.704	D	0.441	neutral	None	None	None	None	N
H/W	0.3874	ambiguous	0.3614	ambiguous	0.952	Stabilizing	0.985	D	0.467	neutral	None	None	None	None	N
H/Y	0.1024	likely_benign	0.0975	benign	1.122	Stabilizing	0.002	N	0.148	neutral	N	0.475594816	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.