TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8122	24589;24590;24591	chr2:178718836;178718835;178718834	chr2:179583563;179583562;179583561
N2AB	7805	23638;23639;23640	chr2:178718836;178718835;178718834	chr2:179583563;179583562;179583561
N2A	6878	20857;20858;20859	chr2:178718836;178718835;178718834	chr2:179583563;179583562;179583561
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-66
• Domain position: 45
• Structural Position: 102
• Q(SASA): 0.8487
• 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/K	None	None	None	N	0.137	0.143	0.159798565429	gnomAD-4.0.0	1.59132E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-05	0
E/V	rs757736721	0.359	0.081	N	0.215	0.144	0.256793551483	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.67E-05	0
E/V	rs757736721	0.359	0.081	N	0.215	0.144	0.256793551483	gnomAD-4.0.0	4.77386E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.5751E-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	0.1051	likely_benign	0.0995	benign	-0.014	Destabilizing	0.019	N	0.243	neutral	N	0.43760407	None	None	N
E/C	0.6441	likely_pathogenic	0.6275	pathogenic	-0.388	Destabilizing	0.958	D	0.195	neutral	None	None	None	None	N
E/D	0.0765	likely_benign	0.0694	benign	-0.545	Destabilizing	None	N	0.147	neutral	N	0.395005299	None	None	N
E/F	0.449	ambiguous	0.4219	ambiguous	-0.081	Destabilizing	0.859	D	0.245	neutral	None	None	None	None	N
E/G	0.0899	likely_benign	0.0884	benign	-0.085	Destabilizing	0.042	N	0.243	neutral	N	0.441084306	None	None	N
E/H	0.2379	likely_benign	0.2248	benign	0.559	Stabilizing	0.667	D	0.221	neutral	None	None	None	None	N
E/I	0.2073	likely_benign	0.1911	benign	0.116	Stabilizing	0.22	N	0.308	neutral	None	None	None	None	N
E/K	0.0764	likely_benign	0.0729	benign	0.228	Stabilizing	None	N	0.137	neutral	N	0.44955186	None	None	N
E/L	0.2366	likely_benign	0.2252	benign	0.116	Stabilizing	0.104	N	0.211	neutral	None	None	None	None	N
E/M	0.2983	likely_benign	0.2807	benign	-0.14	Destabilizing	0.859	D	0.225	neutral	None	None	None	None	N
E/N	0.1297	likely_benign	0.1165	benign	-0.034	Destabilizing	0.055	N	0.216	neutral	None	None	None	None	N
E/P	0.2067	likely_benign	0.1964	benign	0.087	Stabilizing	None	N	0.13	neutral	None	None	None	None	N
E/Q	0.098	likely_benign	0.0959	benign	-0.024	Destabilizing	0.008	N	0.193	neutral	N	0.452669523	None	None	N
E/R	0.1201	likely_benign	0.1187	benign	0.421	Stabilizing	0.124	N	0.237	neutral	None	None	None	None	N
E/S	0.1065	likely_benign	0.0978	benign	-0.127	Destabilizing	0.002	N	0.126	neutral	None	None	None	None	N
E/T	0.1369	likely_benign	0.1282	benign	-0.052	Destabilizing	0.002	N	0.129	neutral	None	None	None	None	N
E/V	0.1391	likely_benign	0.1326	benign	0.087	Stabilizing	0.081	N	0.215	neutral	N	0.469793847	None	None	N
E/W	0.6434	likely_pathogenic	0.6256	pathogenic	-0.071	Destabilizing	0.958	D	0.202	neutral	None	None	None	None	N
E/Y	0.3284	likely_benign	0.3137	benign	0.113	Stabilizing	0.859	D	0.276	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.