TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13790	41593;41594;41595	chr2:178636203;178636202;178636201	chr2:179500930;179500929;179500928
N2AB	12149	36670;36671;36672	chr2:178636203;178636202;178636201	chr2:179500930;179500929;179500928
N2A	11222	33889;33890;33891	chr2:178636203;178636202;178636201	chr2:179500930;179500929;179500928
N2B	4725	14398;14399;14400	chr2:178636203;178636202;178636201	chr2:179500930;179500929;179500928
Novex-1	4850	14773;14774;14775	chr2:178636203;178636202;178636201	chr2:179500930;179500929;179500928
Novex-2	4917	14974;14975;14976	chr2:178636203;178636202;178636201	chr2:179500930;179500929;179500928
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-88
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.6709
• 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	0.101	N	0.287	0.139	0.238096912614	gnomAD-4.0.0	1.37878E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80965E-06	0	0
V/G	None	None	0.351	N	0.648	0.142	0.397391247328	gnomAD-4.0.0	6.8939E-07	None	None	None	None	N	None	0	0	None	0	0	None	1.88388E-05	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	0.5633	ambiguous	0.666	pathogenic	-1.354	Destabilizing	0.101	N	0.287	neutral	N	0.327155615	None	None	N
V/C	0.9292	likely_pathogenic	0.9395	pathogenic	-1.048	Destabilizing	0.983	D	0.389	neutral	None	None	None	None	N
V/D	0.829	likely_pathogenic	0.8774	pathogenic	-1.155	Destabilizing	0.213	N	0.655	prob.neutral	N	0.379527999	None	None	N
V/E	0.6319	likely_pathogenic	0.7152	pathogenic	-1.174	Destabilizing	0.002	N	0.331	neutral	None	None	None	None	N
V/F	0.4326	ambiguous	0.5306	ambiguous	-1.064	Destabilizing	0.655	D	0.527	neutral	N	0.414191682	None	None	N
V/G	0.6219	likely_pathogenic	0.6902	pathogenic	-1.654	Destabilizing	0.351	N	0.648	neutral	N	0.414810211	None	None	N
V/H	0.8995	likely_pathogenic	0.9298	pathogenic	-1.165	Destabilizing	0.951	D	0.545	neutral	None	None	None	None	N
V/I	0.1156	likely_benign	0.126	benign	-0.644	Destabilizing	0.007	N	0.193	neutral	N	0.347634273	None	None	N
V/K	0.7078	likely_pathogenic	0.7735	pathogenic	-1.216	Destabilizing	0.264	N	0.557	neutral	None	None	None	None	N
V/L	0.5552	ambiguous	0.6314	pathogenic	-0.644	Destabilizing	0.001	N	0.074	neutral	N	0.34901194	None	None	N
V/M	0.3178	likely_benign	0.3798	ambiguous	-0.538	Destabilizing	0.061	N	0.281	neutral	None	None	None	None	N
V/N	0.6791	likely_pathogenic	0.7436	pathogenic	-0.975	Destabilizing	0.716	D	0.667	prob.neutral	None	None	None	None	N
V/P	0.9812	likely_pathogenic	0.9854	pathogenic	-0.845	Destabilizing	0.836	D	0.614	neutral	None	None	None	None	N
V/Q	0.6668	likely_pathogenic	0.7317	pathogenic	-1.163	Destabilizing	0.557	D	0.626	neutral	None	None	None	None	N
V/R	0.7187	likely_pathogenic	0.7785	pathogenic	-0.665	Destabilizing	0.716	D	0.677	prob.neutral	None	None	None	None	N
V/S	0.6962	likely_pathogenic	0.7682	pathogenic	-1.487	Destabilizing	0.264	N	0.492	neutral	None	None	None	None	N
V/T	0.4627	ambiguous	0.5341	ambiguous	-1.394	Destabilizing	0.004	N	0.069	neutral	None	None	None	None	N
V/W	0.9661	likely_pathogenic	0.9766	pathogenic	-1.209	Destabilizing	0.983	D	0.554	neutral	None	None	None	None	N
V/Y	0.8158	likely_pathogenic	0.8594	pathogenic	-0.938	Destabilizing	0.836	D	0.477	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.