TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4648	14167;14168;14169	chr2:178739291;178739290;178739289	chr2:179604018;179604017;179604016
N2AB	4331	13216;13217;13218	chr2:178739291;178739290;178739289	chr2:179604018;179604017;179604016
N2A	None	None	chr2:None	chr2:None
N2B	4285	13078;13079;13080	chr2:178739291;178739290;178739289	chr2:179604018;179604017;179604016
Novex-1	4410	13453;13454;13455	chr2:178739291;178739290;178739289	chr2:179604018;179604017;179604016
Novex-2	4477	13654;13655;13656	chr2:178739291;178739290;178739289	chr2:179604018;179604017;179604016
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-29
• Domain position: 43
• Structural Position: 102
• Q(SASA): 0.7238
• 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	rs1372025302	None	None	N	0.131	0.089	0.431490205687	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/A	rs1372025302	None	None	N	0.131	0.089	0.431490205687	gnomAD-4.0.0	4.95986E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.78383E-06	0	0
E/Q	None	None	None	N	0.211	0.067	0.341460817117	gnomAD-4.0.0	1.59332E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86239E-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
E/A	0.1019	likely_benign	0.108	benign	-0.026	Destabilizing	None	N	0.131	neutral	N	0.449979726	None	None	N
E/C	0.6047	likely_pathogenic	0.6249	pathogenic	-0.102	Destabilizing	0.676	D	0.17	neutral	None	None	None	None	N
E/D	0.1006	likely_benign	0.1029	benign	-0.168	Destabilizing	0.012	N	0.183	neutral	N	0.440456973	None	None	N
E/F	0.505	ambiguous	0.5392	ambiguous	-0.101	Destabilizing	0.214	N	0.245	neutral	None	None	None	None	N
E/G	0.0695	likely_benign	0.0704	benign	-0.137	Destabilizing	None	N	0.132	neutral	N	0.437191187	None	None	N
E/H	0.2485	likely_benign	0.2664	benign	0.458	Stabilizing	0.214	N	0.185	neutral	None	None	None	None	N
E/I	0.2272	likely_benign	0.2463	benign	0.208	Stabilizing	None	N	0.22	neutral	None	None	None	None	N
E/K	0.0638	likely_benign	0.064	benign	0.425	Stabilizing	None	N	0.085	neutral	N	0.429990731	None	None	N
E/L	0.2266	likely_benign	0.2516	benign	0.208	Stabilizing	0.016	N	0.233	neutral	None	None	None	None	N
E/M	0.2621	likely_benign	0.2881	benign	0.037	Stabilizing	0.214	N	0.197	neutral	None	None	None	None	N
E/N	0.1396	likely_benign	0.1515	benign	0.286	Stabilizing	None	N	0.155	neutral	None	None	None	None	N
E/P	0.2555	likely_benign	0.2871	benign	0.148	Stabilizing	0.136	N	0.267	neutral	None	None	None	None	N
E/Q	0.0923	likely_benign	0.0967	benign	0.285	Stabilizing	None	N	0.211	neutral	N	0.449346681	None	None	N
E/R	0.1062	likely_benign	0.1133	benign	0.627	Stabilizing	0.016	N	0.171	neutral	None	None	None	None	N
E/S	0.1111	likely_benign	0.1196	benign	0.105	Stabilizing	0.007	N	0.145	neutral	None	None	None	None	N
E/T	0.1272	likely_benign	0.1368	benign	0.201	Stabilizing	0.031	N	0.261	neutral	None	None	None	None	N
E/V	0.1515	likely_benign	0.1632	benign	0.148	Stabilizing	0.012	N	0.196	neutral	N	0.480818406	None	None	N
E/W	0.6108	likely_pathogenic	0.6505	pathogenic	-0.064	Destabilizing	0.864	D	0.18	neutral	None	None	None	None	N
E/Y	0.3659	ambiguous	0.3909	ambiguous	0.121	Stabilizing	0.356	N	0.251	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.