TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17493	52702;52703;52704	chr2:178608406;178608405;178608404	chr2:179473133;179473132;179473131
N2AB	15852	47779;47780;47781	chr2:178608406;178608405;178608404	chr2:179473133;179473132;179473131
N2A	14925	44998;44999;45000	chr2:178608406;178608405;178608404	chr2:179473133;179473132;179473131
N2B	8428	25507;25508;25509	chr2:178608406;178608405;178608404	chr2:179473133;179473132;179473131
Novex-1	8553	25882;25883;25884	chr2:178608406;178608405;178608404	chr2:179473133;179473132;179473131
Novex-2	8620	26083;26084;26085	chr2:178608406;178608405;178608404	chr2:179473133;179473132;179473131
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: Fn3-15
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.5185
• 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	rs2055442864	None	0.998	N	0.685	0.356	0.425615883737	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
E/G	rs2055442864	None	0.998	N	0.685	0.356	0.425615883737	gnomAD-4.0.0	6.57843E-06	None	None	None	None	N	None	0	6.55566E-05	None	0	0	None	0	0	0	0	0
E/Q	rs1046078803	-0.534	0.998	N	0.567	0.223	0.250579442822	gnomAD-2.1.1	4.14E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.18E-06	0
E/Q	rs1046078803	-0.534	0.998	N	0.567	0.223	0.250579442822	gnomAD-4.0.0	8.00538E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.14943E-05	0	3.03841E-05

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	0.1606	likely_benign	0.1514	benign	-0.211	Destabilizing	0.989	D	0.545	neutral	N	0.431147819	None	None	N
E/C	0.8478	likely_pathogenic	0.8464	pathogenic	-0.46	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/D	0.3795	ambiguous	0.3452	ambiguous	-0.857	Destabilizing	0.998	D	0.437	neutral	N	0.502954776	None	None	N
E/F	0.8144	likely_pathogenic	0.7988	pathogenic	0.344	Stabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
E/G	0.3219	likely_benign	0.3096	benign	-0.497	Destabilizing	0.998	D	0.685	prob.neutral	N	0.504050854	None	None	N
E/H	0.6298	likely_pathogenic	0.615	pathogenic	0.651	Stabilizing	1.0	D	0.606	neutral	None	None	None	None	N
E/I	0.2841	likely_benign	0.2723	benign	0.546	Stabilizing	0.995	D	0.755	deleterious	None	None	None	None	N
E/K	0.1183	likely_benign	0.1184	benign	-0.054	Destabilizing	0.994	D	0.455	neutral	N	0.475613459	None	None	N
E/L	0.3972	ambiguous	0.3813	ambiguous	0.546	Stabilizing	0.983	D	0.618	neutral	None	None	None	None	N
E/M	0.4328	ambiguous	0.4185	ambiguous	0.371	Stabilizing	0.96	D	0.434	neutral	None	None	None	None	N
E/N	0.5387	ambiguous	0.5067	ambiguous	-0.605	Destabilizing	1.0	D	0.619	neutral	None	None	None	None	N
E/P	0.3466	ambiguous	0.3498	ambiguous	0.314	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/Q	0.1526	likely_benign	0.1469	benign	-0.468	Destabilizing	0.998	D	0.567	neutral	N	0.479808557	None	None	N
E/R	0.2445	likely_benign	0.2404	benign	0.377	Stabilizing	0.999	D	0.617	neutral	None	None	None	None	N
E/S	0.3492	ambiguous	0.3316	benign	-0.806	Destabilizing	0.996	D	0.531	neutral	None	None	None	None	N
E/T	0.3003	likely_benign	0.2815	benign	-0.547	Destabilizing	0.999	D	0.704	prob.neutral	None	None	None	None	N
E/V	0.1649	likely_benign	0.1602	benign	0.314	Stabilizing	0.978	D	0.643	neutral	N	0.502530701	None	None	N
E/W	0.957	likely_pathogenic	0.9518	pathogenic	0.529	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/Y	0.7175	likely_pathogenic	0.6981	pathogenic	0.606	Stabilizing	1.0	D	0.777	deleterious	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.