TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14917	44974;44975;44976	chr2:178624531;178624530;178624529	chr2:179489258;179489257;179489256
N2AB	13276	40051;40052;40053	chr2:178624531;178624530;178624529	chr2:179489258;179489257;179489256
N2A	12349	37270;37271;37272	chr2:178624531;178624530;178624529	chr2:179489258;179489257;179489256
N2B	5852	17779;17780;17781	chr2:178624531;178624530;178624529	chr2:179489258;179489257;179489256
Novex-1	5977	18154;18155;18156	chr2:178624531;178624530;178624529	chr2:179489258;179489257;179489256
Novex-2	6044	18355;18356;18357	chr2:178624531;178624530;178624529	chr2:179489258;179489257;179489256
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-100
• Domain position: 65
• Structural Position: 148
• Q(SASA): 0.6651
• 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/G	None	None	0.822	N	0.483	0.243	0.20549828249	gnomAD-4.0.0	4.79232E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29927E-06	0	0
E/K	None	None	0.822	N	0.467	0.293	0.191931220699	gnomAD-4.0.0	2.05386E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.87329E-05	0	1.79978E-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	0.1618	likely_benign	0.1541	benign	-0.299	Destabilizing	0.822	D	0.473	neutral	N	0.346214157	None	None	N
E/C	0.9211	likely_pathogenic	0.9254	pathogenic	-0.059	Destabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	N
E/D	0.1195	likely_benign	0.096	benign	-0.251	Destabilizing	0.002	N	0.169	neutral	N	0.34444924	None	None	N
E/F	0.8215	likely_pathogenic	0.8297	pathogenic	-0.248	Destabilizing	0.993	D	0.62	neutral	None	None	None	None	N
E/G	0.1834	likely_benign	0.1521	benign	-0.474	Destabilizing	0.822	D	0.483	neutral	N	0.331881853	None	None	N
E/H	0.5753	likely_pathogenic	0.5628	ambiguous	0.082	Stabilizing	0.993	D	0.411	neutral	None	None	None	None	N
E/I	0.5727	likely_pathogenic	0.548	ambiguous	0.121	Stabilizing	0.978	D	0.613	neutral	None	None	None	None	N
E/K	0.1821	likely_benign	0.1733	benign	0.294	Stabilizing	0.822	D	0.467	neutral	N	0.323734882	None	None	N
E/L	0.5446	ambiguous	0.5216	ambiguous	0.121	Stabilizing	0.978	D	0.593	neutral	None	None	None	None	N
E/M	0.6025	likely_pathogenic	0.6013	pathogenic	0.15	Stabilizing	0.998	D	0.585	neutral	None	None	None	None	N
E/N	0.3152	likely_benign	0.2724	benign	0.065	Stabilizing	0.754	D	0.433	neutral	None	None	None	None	N
E/P	0.8095	likely_pathogenic	0.8274	pathogenic	0.001	Stabilizing	0.978	D	0.436	neutral	None	None	None	None	N
E/Q	0.2052	likely_benign	0.1876	benign	0.092	Stabilizing	0.904	D	0.408	neutral	N	0.335468128	None	None	N
E/R	0.3111	likely_benign	0.3117	benign	0.518	Stabilizing	0.978	D	0.409	neutral	None	None	None	None	N
E/S	0.235	likely_benign	0.2056	benign	-0.117	Destabilizing	0.86	D	0.45	neutral	None	None	None	None	N
E/T	0.3057	likely_benign	0.2935	benign	0.024	Stabilizing	0.86	D	0.442	neutral	None	None	None	None	N
E/V	0.3594	ambiguous	0.3415	ambiguous	0.001	Stabilizing	0.97	D	0.497	neutral	N	0.38665426	None	None	N
E/W	0.9087	likely_pathogenic	0.9136	pathogenic	-0.135	Destabilizing	0.998	D	0.722	prob.delet.	None	None	None	None	N
E/Y	0.7056	likely_pathogenic	0.7147	pathogenic	-0.017	Destabilizing	0.993	D	0.579	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.