TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16433	49522;49523;49524	chr2:178614100;178614099;178614098	chr2:179478827;179478826;179478825
N2AB	14792	44599;44600;44601	chr2:178614100;178614099;178614098	chr2:179478827;179478826;179478825
N2A	13865	41818;41819;41820	chr2:178614100;178614099;178614098	chr2:179478827;179478826;179478825
N2B	7368	22327;22328;22329	chr2:178614100;178614099;178614098	chr2:179478827;179478826;179478825
Novex-1	7493	22702;22703;22704	chr2:178614100;178614099;178614098	chr2:179478827;179478826;179478825
Novex-2	7560	22903;22904;22905	chr2:178614100;178614099;178614098	chr2:179478827;179478826;179478825
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-6
• Domain position: 83
• Structural Position: 117
• Q(SASA): 0.509
• 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	0.822	N	0.599	0.214	0.569670436194	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	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	0.2681	likely_benign	0.2422	benign	-1.056	Destabilizing	0.822	D	0.599	neutral	N	0.481119261	None	None	N
V/C	0.788	likely_pathogenic	0.7636	pathogenic	-0.729	Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
V/D	0.747	likely_pathogenic	0.6755	pathogenic	-0.875	Destabilizing	0.99	D	0.819	deleterious	N	0.475286505	None	None	N
V/E	0.5599	ambiguous	0.4931	ambiguous	-0.97	Destabilizing	0.993	D	0.801	deleterious	None	None	None	None	N
V/F	0.2689	likely_benign	0.245	benign	-1.117	Destabilizing	0.942	D	0.774	deleterious	N	0.48132334	None	None	N
V/G	0.5118	ambiguous	0.4455	ambiguous	-1.255	Destabilizing	0.971	D	0.801	deleterious	N	0.513289526	None	None	N
V/H	0.7948	likely_pathogenic	0.7429	pathogenic	-0.714	Destabilizing	0.998	D	0.809	deleterious	None	None	None	None	N
V/I	0.0658	likely_benign	0.0678	benign	-0.655	Destabilizing	0.014	N	0.258	neutral	N	0.443792252	None	None	N
V/K	0.5712	likely_pathogenic	0.4936	ambiguous	-0.773	Destabilizing	0.978	D	0.805	deleterious	None	None	None	None	N
V/L	0.2849	likely_benign	0.2625	benign	-0.655	Destabilizing	0.247	N	0.531	neutral	N	0.465115061	None	None	N
V/M	0.186	likely_benign	0.1829	benign	-0.427	Destabilizing	0.956	D	0.781	deleterious	None	None	None	None	N
V/N	0.5248	ambiguous	0.4573	ambiguous	-0.445	Destabilizing	0.993	D	0.817	deleterious	None	None	None	None	N
V/P	0.6941	likely_pathogenic	0.6401	pathogenic	-0.753	Destabilizing	0.993	D	0.812	deleterious	None	None	None	None	N
V/Q	0.5249	ambiguous	0.4687	ambiguous	-0.761	Destabilizing	0.993	D	0.811	deleterious	None	None	None	None	N
V/R	0.4975	ambiguous	0.4325	ambiguous	-0.138	Destabilizing	0.993	D	0.816	deleterious	None	None	None	None	N
V/S	0.4149	ambiguous	0.3681	ambiguous	-0.873	Destabilizing	0.978	D	0.795	deleterious	None	None	None	None	N
V/T	0.2087	likely_benign	0.191	benign	-0.871	Destabilizing	0.86	D	0.727	prob.delet.	None	None	None	None	N
V/W	0.8954	likely_pathogenic	0.879	pathogenic	-1.156	Destabilizing	0.998	D	0.787	deleterious	None	None	None	None	N
V/Y	0.7245	likely_pathogenic	0.6773	pathogenic	-0.887	Destabilizing	0.978	D	0.783	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.