TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30611	92056;92057;92058	chr2:178550007;178550006;178550005	chr2:179414734;179414733;179414732
N2AB	28970	87133;87134;87135	chr2:178550007;178550006;178550005	chr2:179414734;179414733;179414732
N2A	28043	84352;84353;84354	chr2:178550007;178550006;178550005	chr2:179414734;179414733;179414732
N2B	21546	64861;64862;64863	chr2:178550007;178550006;178550005	chr2:179414734;179414733;179414732
Novex-1	21671	65236;65237;65238	chr2:178550007;178550006;178550005	chr2:179414734;179414733;179414732
Novex-2	21738	65437;65438;65439	chr2:178550007;178550006;178550005	chr2:179414734;179414733;179414732
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-149
• Domain position: 80
• Structural Position: 171
• Q(SASA): 0.2834
• 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
E/A	None	None	0.027	N	0.457	0.24	0.281381271821	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/K	rs769702560	-0.068	0.027	N	0.367	0.137	0.241664281697	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.34E-05	None	0	0	0
E/K	rs769702560	-0.068	0.027	N	0.367	0.137	0.241664281697	gnomAD-4.0.0	1.37352E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.33465E-05	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
E/A	0.1115	likely_benign	0.1228	benign	-0.388	Destabilizing	0.027	N	0.457	neutral	N	0.441322819	None	None	N
E/C	0.6421	likely_pathogenic	0.6927	pathogenic	-0.14	Destabilizing	0.935	D	0.625	neutral	None	None	None	None	N
E/D	0.0743	likely_benign	0.0891	benign	-0.404	Destabilizing	None	N	0.122	neutral	N	0.437821154	None	None	N
E/F	0.5653	likely_pathogenic	0.6508	pathogenic	-0.188	Destabilizing	0.791	D	0.606	neutral	None	None	None	None	N
E/G	0.1346	likely_benign	0.1539	benign	-0.606	Destabilizing	0.052	N	0.525	neutral	D	0.524074702	None	None	N
E/H	0.3042	likely_benign	0.3461	ambiguous	0.021	Stabilizing	0.555	D	0.529	neutral	None	None	None	None	N
E/I	0.2201	likely_benign	0.256	benign	0.159	Stabilizing	0.555	D	0.621	neutral	None	None	None	None	N
E/K	0.1379	likely_benign	0.1419	benign	0.207	Stabilizing	0.027	N	0.367	neutral	N	0.484129447	None	None	N
E/L	0.2831	likely_benign	0.331	benign	0.159	Stabilizing	0.149	N	0.63	neutral	None	None	None	None	N
E/M	0.3111	likely_benign	0.3526	ambiguous	0.204	Stabilizing	0.824	D	0.585	neutral	None	None	None	None	N
E/N	0.1196	likely_benign	0.16	benign	-0.147	Destabilizing	0.081	N	0.327	neutral	None	None	None	None	N
E/P	0.4853	ambiguous	0.5382	ambiguous	-0.002	Destabilizing	0.262	N	0.583	neutral	None	None	None	None	N
E/Q	0.1127	likely_benign	0.1142	benign	-0.094	Destabilizing	0.002	N	0.201	neutral	N	0.471472368	None	None	N
E/R	0.2305	likely_benign	0.242	benign	0.455	Stabilizing	0.081	N	0.477	neutral	None	None	None	None	N
E/S	0.111	likely_benign	0.1339	benign	-0.312	Destabilizing	0.035	N	0.375	neutral	None	None	None	None	N
E/T	0.1169	likely_benign	0.1328	benign	-0.135	Destabilizing	0.149	N	0.504	neutral	None	None	None	None	N
E/V	0.1393	likely_benign	0.1545	benign	-0.002	Destabilizing	0.117	N	0.619	neutral	N	0.474686031	None	None	N
E/W	0.8044	likely_pathogenic	0.8472	pathogenic	-0.023	Destabilizing	0.935	D	0.669	neutral	None	None	None	None	N
E/Y	0.4457	ambiguous	0.5106	ambiguous	0.054	Stabilizing	0.555	D	0.603	neutral	None	None	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.