TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8273	25042;25043;25044	chr2:178718189;178718188;178718187	chr2:179582916;179582915;179582914
N2AB	7956	24091;24092;24093	chr2:178718189;178718188;178718187	chr2:179582916;179582915;179582914
N2A	7029	21310;21311;21312	chr2:178718189;178718188;178718187	chr2:179582916;179582915;179582914
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: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-68
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.2964
• 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
V/A	None	None	0.002	D	0.103	0.177	0.498705051145	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
V/M	None	None	0.005	N	0.265	0.134	0.183819452728	gnomAD-4.0.0	1.61611E-06	None	None	None	None	N	None	0	2.29474E-05	None	0	0	None	0	0	0	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
V/A	0.1606	likely_benign	0.1582	benign	-1.216	Destabilizing	0.002	N	0.103	neutral	D	0.522191976	None	None	N
V/C	0.7045	likely_pathogenic	0.7179	pathogenic	-0.801	Destabilizing	0.724	D	0.456	neutral	None	None	None	None	N
V/D	0.4151	ambiguous	0.4232	ambiguous	-1.036	Destabilizing	0.475	N	0.547	neutral	None	None	None	None	N
V/E	0.2712	likely_benign	0.2516	benign	-1.056	Destabilizing	0.1	N	0.497	neutral	N	0.507642742	None	None	N
V/F	0.1614	likely_benign	0.1637	benign	-0.943	Destabilizing	0.705	D	0.507	neutral	None	None	None	None	N
V/G	0.2517	likely_benign	0.2715	benign	-1.505	Destabilizing	0.003	N	0.371	neutral	D	0.53158312	None	None	N
V/H	0.4927	ambiguous	0.4848	ambiguous	-1.092	Destabilizing	0.976	D	0.525	neutral	None	None	None	None	N
V/I	0.0765	likely_benign	0.0723	benign	-0.536	Destabilizing	None	N	0.176	neutral	None	None	None	None	N
V/K	0.2323	likely_benign	0.2218	benign	-1.145	Destabilizing	0.242	N	0.497	neutral	None	None	None	None	N
V/L	0.1764	likely_benign	0.1648	benign	-0.536	Destabilizing	0.001	N	0.289	neutral	N	0.520613109	None	None	N
V/M	0.119	likely_benign	0.1108	benign	-0.434	Destabilizing	0.005	N	0.265	neutral	N	0.490828707	None	None	N
V/N	0.3284	likely_benign	0.3131	benign	-0.882	Destabilizing	0.045	N	0.56	neutral	None	None	None	None	N
V/P	0.7891	likely_pathogenic	0.8198	pathogenic	-0.727	Destabilizing	0.253	N	0.562	neutral	None	None	None	None	N
V/Q	0.2452	likely_benign	0.2319	benign	-1.05	Destabilizing	0.617	D	0.545	neutral	None	None	None	None	N
V/R	0.1963	likely_benign	0.2002	benign	-0.634	Destabilizing	0.705	D	0.578	neutral	None	None	None	None	N
V/S	0.2306	likely_benign	0.2246	benign	-1.342	Destabilizing	0.014	N	0.351	neutral	None	None	None	None	N
V/T	0.1487	likely_benign	0.1332	benign	-1.256	Destabilizing	None	N	0.103	neutral	None	None	None	None	N
V/W	0.6951	likely_pathogenic	0.7157	pathogenic	-1.133	Destabilizing	0.993	D	0.559	neutral	None	None	None	None	N
V/Y	0.4939	ambiguous	0.4816	ambiguous	-0.844	Destabilizing	0.829	D	0.463	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.