TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3368	10327;10328;10329	chr2:178764189;178764188;178764187	chr2:179628916;179628915;179628914
N2AB	3368	10327;10328;10329	chr2:178764189;178764188;178764187	chr2:179628916;179628915;179628914
N2A	3368	10327;10328;10329	chr2:178764189;178764188;178764187	chr2:179628916;179628915;179628914
N2B	3322	10189;10190;10191	chr2:178764189;178764188;178764187	chr2:179628916;179628915;179628914
Novex-1	3322	10189;10190;10191	chr2:178764189;178764188;178764187	chr2:179628916;179628915;179628914
Novex-2	3322	10189;10190;10191	chr2:178764189;178764188;178764187	chr2:179628916;179628915;179628914
Novex-3	3368	10327;10328;10329	chr2:178764189;178764188;178764187	chr2:179628916;179628915;179628914

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-24
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.0908
• 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	rs149309988	-2.4	0.999	D	0.614	0.644	None	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	6.15E-05	0	None	0	0	None	0	None	0	0	0
V/A	rs149309988	-2.4	0.999	D	0.614	0.644	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/A	rs149309988	-2.4	0.999	D	0.614	0.644	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
V/A	rs149309988	-2.4	0.999	D	0.614	0.644	None	gnomAD-4.0.0	2.02961E-06	None	None	None	None	N	None	3.48736E-05	0	None	0	0	None	0	0	0	0	0
V/F	None	None	1.0	D	0.851	0.594	0.884733524946	gnomAD-4.0.0	6.84086E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99326E-07	0	0
V/I	rs771921268	-0.363	0.997	N	0.556	0.296	0.552980905328	gnomAD-2.1.1	7.96E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.53E-05	None	0	0	0
V/I	rs771921268	-0.363	0.997	N	0.556	0.296	0.552980905328	gnomAD-4.0.0	4.10452E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79865E-06	4.63725E-05	0
V/L	rs771921268	-0.366	0.997	D	0.629	0.437	0.574945690627	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/L	rs771921268	-0.366	0.997	D	0.629	0.437	0.574945690627	gnomAD-4.0.0	1.2392E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.69495E-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
V/A	0.7317	likely_pathogenic	0.7317	pathogenic	-1.892	Destabilizing	0.999	D	0.614	neutral	D	0.524968634	None	None	N
V/C	0.9755	likely_pathogenic	0.971	pathogenic	-1.453	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/D	0.9951	likely_pathogenic	0.9937	pathogenic	-2.478	Highly Destabilizing	1.0	D	0.857	deleterious	D	0.733439603	None	None	N
V/E	0.9857	likely_pathogenic	0.982	pathogenic	-2.19	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
V/F	0.7462	likely_pathogenic	0.7379	pathogenic	-1.025	Destabilizing	1.0	D	0.851	deleterious	D	0.645610175	None	None	N
V/G	0.8751	likely_pathogenic	0.8704	pathogenic	-2.497	Highly Destabilizing	1.0	D	0.849	deleterious	D	0.674133846	None	None	N
V/H	0.9963	likely_pathogenic	0.9949	pathogenic	-2.389	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
V/I	0.1127	likely_benign	0.112	benign	-0.169	Destabilizing	0.997	D	0.556	neutral	N	0.503133155	None	None	N
V/K	0.9918	likely_pathogenic	0.9896	pathogenic	-1.364	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
V/L	0.5384	ambiguous	0.5803	pathogenic	-0.169	Destabilizing	0.997	D	0.629	neutral	D	0.53598611	None	None	N
V/M	0.6338	likely_pathogenic	0.6245	pathogenic	-0.433	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
V/N	0.9881	likely_pathogenic	0.984	pathogenic	-1.883	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
V/P	0.9919	likely_pathogenic	0.9914	pathogenic	-0.718	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
V/Q	0.9878	likely_pathogenic	0.9843	pathogenic	-1.578	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
V/R	0.9859	likely_pathogenic	0.9818	pathogenic	-1.485	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
V/S	0.9395	likely_pathogenic	0.9299	pathogenic	-2.516	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
V/T	0.8637	likely_pathogenic	0.848	pathogenic	-2.061	Highly Destabilizing	0.999	D	0.649	neutral	None	None	None	None	N
V/W	0.9966	likely_pathogenic	0.9952	pathogenic	-1.58	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/Y	0.9822	likely_pathogenic	0.976	pathogenic	-1.157	Destabilizing	1.0	D	0.855	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.