TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6137	18634;18635;18636	chr2:178729844;178729843;178729842	chr2:179594571;179594570;179594569
N2AB	5820	17683;17684;17685	chr2:178729844;178729843;178729842	chr2:179594571;179594570;179594569
N2A	4893	14902;14903;14904	chr2:178729844;178729843;178729842	chr2:179594571;179594570;179594569
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: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-45
• Domain position: 33
• Structural Position: 46
• Q(SASA): 0.2443
• 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	0.334	D	0.654	0.636	0.685252170855	gnomAD-4.0.0	6.84258E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99493E-07	0	0
V/G	None	None	0.896	D	0.805	0.75	0.878149281796	gnomAD-4.0.0	6.84258E-07	None	None	None	None	N	None	0	0	None	0	2.52143E-05	None	0	0	0	0	0
V/M	None	None	0.81	D	0.649	0.69	0.679255775376	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
V/A	0.5015	ambiguous	0.4356	ambiguous	-1.427	Destabilizing	0.334	N	0.654	neutral	D	0.598927218	None	None	N
V/C	0.9317	likely_pathogenic	0.9098	pathogenic	-0.86	Destabilizing	0.992	D	0.74	deleterious	None	None	None	None	N
V/D	0.9348	likely_pathogenic	0.887	pathogenic	-1.252	Destabilizing	0.92	D	0.831	deleterious	None	None	None	None	N
V/E	0.8726	likely_pathogenic	0.8077	pathogenic	-1.139	Destabilizing	0.896	D	0.798	deleterious	D	0.637314748	None	None	N
V/F	0.4335	ambiguous	0.3583	ambiguous	-0.871	Destabilizing	0.012	N	0.541	neutral	None	None	None	None	N
V/G	0.6275	likely_pathogenic	0.5378	ambiguous	-1.842	Destabilizing	0.896	D	0.805	deleterious	D	0.637314748	None	None	N
V/H	0.9604	likely_pathogenic	0.9355	pathogenic	-1.345	Destabilizing	0.992	D	0.835	deleterious	None	None	None	None	N
V/I	0.091	likely_benign	0.0909	benign	-0.339	Destabilizing	0.002	N	0.279	neutral	None	None	None	None	N
V/K	0.919	likely_pathogenic	0.8662	pathogenic	-1.064	Destabilizing	0.85	D	0.797	deleterious	None	None	None	None	N
V/L	0.4274	ambiguous	0.3717	ambiguous	-0.339	Destabilizing	0.099	N	0.523	neutral	D	0.554130159	None	None	N
V/M	0.3869	ambiguous	0.3182	benign	-0.335	Destabilizing	0.81	D	0.649	neutral	D	0.595121503	None	None	N
V/N	0.8716	likely_pathogenic	0.8065	pathogenic	-1.083	Destabilizing	0.92	D	0.845	deleterious	None	None	None	None	N
V/P	0.8596	likely_pathogenic	0.8114	pathogenic	-0.669	Destabilizing	0.972	D	0.835	deleterious	None	None	None	None	N
V/Q	0.8979	likely_pathogenic	0.8417	pathogenic	-1.066	Destabilizing	0.972	D	0.833	deleterious	None	None	None	None	N
V/R	0.8924	likely_pathogenic	0.8326	pathogenic	-0.792	Destabilizing	0.92	D	0.845	deleterious	None	None	None	None	N
V/S	0.7413	likely_pathogenic	0.6686	pathogenic	-1.677	Destabilizing	0.447	N	0.793	deleterious	None	None	None	None	N
V/T	0.5587	ambiguous	0.4835	ambiguous	-1.426	Destabilizing	0.021	N	0.442	neutral	None	None	None	None	N
V/W	0.9683	likely_pathogenic	0.9471	pathogenic	-1.181	Destabilizing	0.992	D	0.828	deleterious	None	None	None	None	N
V/Y	0.8725	likely_pathogenic	0.814	pathogenic	-0.8	Destabilizing	0.739	D	0.749	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.