TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14382	43369;43370;43371	chr2:178632987;178632986;178632985	chr2:179497714;179497713;179497712
N2AB	12741	38446;38447;38448	chr2:178632987;178632986;178632985	chr2:179497714;179497713;179497712
N2A	11814	35665;35666;35667	chr2:178632987;178632986;178632985	chr2:179497714;179497713;179497712
N2B	5317	16174;16175;16176	chr2:178632987;178632986;178632985	chr2:179497714;179497713;179497712
Novex-1	5442	16549;16550;16551	chr2:178632987;178632986;178632985	chr2:179497714;179497713;179497712
Novex-2	5509	16750;16751;16752	chr2:178632987;178632986;178632985	chr2:179497714;179497713;179497712
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-94
• Domain position: 64
• Structural Position: 146
• Q(SASA): 0.3254
• 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
L/Q	None	None	0.988	D	0.641	0.457	0.575880570741	gnomAD-4.0.0	1.59257E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86074E-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
L/A	0.2183	likely_benign	0.1918	benign	-1.125	Destabilizing	0.938	D	0.471	neutral	None	None	None	None	N
L/C	0.7427	likely_pathogenic	0.7019	pathogenic	-0.765	Destabilizing	0.999	D	0.448	neutral	None	None	None	None	N
L/D	0.6332	likely_pathogenic	0.5867	pathogenic	-0.424	Destabilizing	0.997	D	0.727	deleterious	None	None	None	None	N
L/E	0.2809	likely_benign	0.2541	benign	-0.491	Destabilizing	0.997	D	0.713	prob.delet.	None	None	None	None	N
L/F	0.2577	likely_benign	0.2158	benign	-0.946	Destabilizing	0.991	D	0.417	neutral	None	None	None	None	N
L/G	0.6118	likely_pathogenic	0.5447	ambiguous	-1.349	Destabilizing	0.991	D	0.696	prob.delet.	None	None	None	None	N
L/H	0.3274	likely_benign	0.298	benign	-0.552	Destabilizing	0.999	D	0.758	deleterious	None	None	None	None	N
L/I	0.1042	likely_benign	0.0935	benign	-0.632	Destabilizing	0.757	D	0.373	neutral	None	None	None	None	N
L/K	0.2834	likely_benign	0.2632	benign	-0.654	Destabilizing	0.991	D	0.529	neutral	None	None	None	None	N
L/M	0.1694	likely_benign	0.1463	benign	-0.508	Destabilizing	0.506	D	0.422	neutral	N	0.438986668	None	None	N
L/N	0.4242	ambiguous	0.3914	ambiguous	-0.42	Destabilizing	0.997	D	0.745	deleterious	None	None	None	None	N
L/P	0.1882	likely_benign	0.1659	benign	-0.762	Destabilizing	0.996	D	0.72	deleterious	N	0.437427935	None	None	N
L/Q	0.1933	likely_benign	0.1797	benign	-0.664	Destabilizing	0.988	D	0.641	neutral	D	0.546790564	None	None	N
L/R	0.2466	likely_benign	0.2182	benign	-0.039	Destabilizing	0.988	D	0.647	neutral	N	0.416400984	None	None	N
L/S	0.2993	likely_benign	0.2605	benign	-0.967	Destabilizing	0.991	D	0.492	neutral	None	None	None	None	N
L/T	0.1982	likely_benign	0.1791	benign	-0.923	Destabilizing	0.938	D	0.491	neutral	None	None	None	None	N
L/V	0.1186	likely_benign	0.1082	benign	-0.762	Destabilizing	0.06	N	0.197	neutral	N	0.435933819	None	None	N
L/W	0.4443	ambiguous	0.3875	ambiguous	-0.933	Destabilizing	0.999	D	0.733	deleterious	None	None	None	None	N
L/Y	0.5105	ambiguous	0.4588	ambiguous	-0.707	Destabilizing	0.997	D	0.38	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.