TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9499	28720;28721;28722	chr2:178709824;178709823;178709822	chr2:179574551;179574550;179574549
N2AB	9182	27769;27770;27771	chr2:178709824;178709823;178709822	chr2:179574551;179574550;179574549
N2A	8255	24988;24989;24990	chr2:178709824;178709823;178709822	chr2:179574551;179574550;179574549
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: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-81
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.6867
• Predicted PPI site: I

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/F	rs1060500573	None	0.998	None	0.492	0.265	0.396794106654	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/F	rs1060500573	None	0.998	None	0.492	0.265	0.396794106654	gnomAD-4.0.0	3.10111E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.69604E-06	2.19833E-05	1.60236E-05
L/P	None	None	0.031	None	0.352	0.175	0.586326688876	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.8245	likely_pathogenic	0.9027	pathogenic	-1.987	Destabilizing	0.97	D	0.521	neutral	None	None	None	None	I
L/C	0.8955	likely_pathogenic	0.9446	pathogenic	-1.435	Destabilizing	1.0	D	0.575	neutral	None	None	None	None	I
L/D	0.9899	likely_pathogenic	0.9973	pathogenic	-0.799	Destabilizing	0.996	D	0.607	neutral	None	None	None	None	I
L/E	0.9675	likely_pathogenic	0.9905	pathogenic	-0.697	Destabilizing	0.996	D	0.56	neutral	None	None	None	None	I
L/F	0.4287	ambiguous	0.6436	pathogenic	-1.206	Destabilizing	0.998	D	0.492	neutral	None	None	None	None	I
L/G	0.9543	likely_pathogenic	0.982	pathogenic	-2.419	Highly Destabilizing	0.996	D	0.533	neutral	None	None	None	None	I
L/H	0.9266	likely_pathogenic	0.9804	pathogenic	-1.537	Destabilizing	1.0	D	0.626	neutral	None	None	None	None	I
L/I	0.1707	likely_benign	0.2331	benign	-0.821	Destabilizing	0.993	D	0.489	neutral	None	None	None	None	I
L/K	0.957	likely_pathogenic	0.9879	pathogenic	-1.222	Destabilizing	0.996	D	0.515	neutral	None	None	None	None	I
L/M	0.2572	likely_benign	0.369	ambiguous	-0.778	Destabilizing	0.999	D	0.512	neutral	None	None	None	None	I
L/N	0.9502	likely_pathogenic	0.985	pathogenic	-1.158	Destabilizing	0.999	D	0.619	neutral	None	None	None	None	I
L/P	0.4267	ambiguous	0.655	pathogenic	-1.181	Destabilizing	0.031	N	0.352	neutral	None	None	None	None	I
L/Q	0.8926	likely_pathogenic	0.9693	pathogenic	-1.169	Destabilizing	0.999	D	0.617	neutral	None	None	None	None	I
L/R	0.9296	likely_pathogenic	0.9788	pathogenic	-0.834	Destabilizing	0.998	D	0.621	neutral	None	None	None	None	I
L/S	0.9457	likely_pathogenic	0.9839	pathogenic	-2.024	Highly Destabilizing	0.996	D	0.509	neutral	None	None	None	None	I
L/T	0.8559	likely_pathogenic	0.939	pathogenic	-1.775	Destabilizing	0.985	D	0.535	neutral	None	None	None	None	I
L/V	0.2371	likely_benign	0.3467	ambiguous	-1.181	Destabilizing	0.98	D	0.497	neutral	None	None	None	None	I
L/W	0.8503	likely_pathogenic	0.9546	pathogenic	-1.27	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
L/Y	0.9076	likely_pathogenic	0.973	pathogenic	-1.048	Destabilizing	0.999	D	0.571	neutral	None	None	None	None	I

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.