TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28575	85948;85949;85950	chr2:178560409;178560408;178560407	chr2:179425136;179425135;179425134
N2AB	26934	81025;81026;81027	chr2:178560409;178560408;178560407	chr2:179425136;179425135;179425134
N2A	26007	78244;78245;78246	chr2:178560409;178560408;178560407	chr2:179425136;179425135;179425134
N2B	19510	58753;58754;58755	chr2:178560409;178560408;178560407	chr2:179425136;179425135;179425134
Novex-1	19635	59128;59129;59130	chr2:178560409;178560408;178560407	chr2:179425136;179425135;179425134
Novex-2	19702	59329;59330;59331	chr2:178560409;178560408;178560407	chr2:179425136;179425135;179425134
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-96
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.867
• 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
E/D	rs752650483	0.003	0.007	N	0.194	0.035	0.222439326576	gnomAD-2.1.1	7.15E-06	None	None	None	None	I	None	4.13E-05	0	None	9.68E-05	0	None	0	None	0	0	0
E/D	rs752650483	0.003	0.007	N	0.194	0.035	0.222439326576	gnomAD-4.0.0	1.59153E-06	None	None	None	None	I	None	0	0	None	4.7669E-05	0	None	0	0	0	0	0
E/G	rs1703193280	None	0.684	N	0.465	0.162	0.330331372229	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/G	rs1703193280	None	0.684	N	0.465	0.162	0.330331372229	gnomAD-4.0.0	6.57376E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47024E-05	0	0
E/K	rs760762822	0.773	0.037	N	0.193	0.132	0.232513804876	gnomAD-2.1.1	3.93E-05	None	None	None	None	I	None	4.13E-05	0	None	0	0	None	0	None	0	7.83E-05	0
E/K	rs760762822	0.773	0.037	N	0.193	0.132	0.232513804876	gnomAD-3.1.2	3.94E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	5.88E-05	0	0
E/K	rs760762822	0.773	0.037	N	0.193	0.132	0.232513804876	gnomAD-4.0.0	5.70177E-05	None	None	None	None	I	None	2.67073E-05	0	None	0	2.23105E-05	None	1.56353E-05	0	7.28943E-05	0	3.20256E-05

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
E/A	0.0857	likely_benign	0.0846	benign	-0.125	Destabilizing	0.309	N	0.366	neutral	N	0.448485573	None	None	I
E/C	0.6138	likely_pathogenic	0.5934	pathogenic	0.195	Stabilizing	0.996	D	0.291	neutral	None	None	None	None	I
E/D	0.0907	likely_benign	0.0902	benign	-0.177	Destabilizing	0.007	N	0.194	neutral	N	0.465340537	None	None	I
E/F	0.4827	ambiguous	0.4758	ambiguous	-0.196	Destabilizing	0.953	D	0.359	neutral	None	None	None	None	I
E/G	0.1046	likely_benign	0.1042	benign	-0.266	Destabilizing	0.684	D	0.465	neutral	N	0.485505166	None	None	I
E/H	0.263	likely_benign	0.2512	benign	0.095	Stabilizing	0.953	D	0.332	neutral	None	None	None	None	I
E/I	0.1649	likely_benign	0.1666	benign	0.192	Stabilizing	0.037	N	0.311	neutral	None	None	None	None	I
E/K	0.0842	likely_benign	0.0838	benign	0.637	Stabilizing	0.037	N	0.193	neutral	N	0.495738015	None	None	I
E/L	0.183	likely_benign	0.1816	benign	0.192	Stabilizing	0.373	N	0.384	neutral	None	None	None	None	I
E/M	0.2615	likely_benign	0.262	benign	0.245	Stabilizing	0.953	D	0.333	neutral	None	None	None	None	I
E/N	0.154	likely_benign	0.1529	benign	0.403	Stabilizing	0.59	D	0.344	neutral	None	None	None	None	I
E/P	0.3001	likely_benign	0.299	benign	0.106	Stabilizing	0.953	D	0.373	neutral	None	None	None	None	I
E/Q	0.0972	likely_benign	0.0961	benign	0.415	Stabilizing	0.846	D	0.36	neutral	N	0.503032134	None	None	I
E/R	0.1427	likely_benign	0.1394	benign	0.703	Stabilizing	0.59	D	0.348	neutral	None	None	None	None	I
E/S	0.1171	likely_benign	0.1172	benign	0.272	Stabilizing	0.742	D	0.34	neutral	None	None	None	None	I
E/T	0.1283	likely_benign	0.1289	benign	0.393	Stabilizing	0.742	D	0.449	neutral	None	None	None	None	I
E/V	0.104	likely_benign	0.1046	benign	0.106	Stabilizing	0.012	N	0.188	neutral	N	0.469978353	None	None	I
E/W	0.7214	likely_pathogenic	0.6882	pathogenic	-0.132	Destabilizing	0.996	D	0.348	neutral	None	None	None	None	I
E/Y	0.3661	ambiguous	0.3562	ambiguous	0.038	Stabilizing	0.984	D	0.372	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.