TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5070	15433;15434;15435	chr2:178734716;178734715;178734714	chr2:179599443;179599442;179599441
N2AB	4753	14482;14483;14484	chr2:178734716;178734715;178734714	chr2:179599443;179599442;179599441
N2A	3826	11701;11702;11703	chr2:178734716;178734715;178734714	chr2:179599443;179599442;179599441
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: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-33
• Domain position: 90
• Structural Position: 175
• Q(SASA): 0.3696
• 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/L	None	None	0.454	N	0.346	0.059	0.476051820916	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	0.2032	likely_benign	0.1723	benign	-1.308	Destabilizing	0.022	N	0.077	neutral	N	0.496622385	None	None	N
V/C	0.7512	likely_pathogenic	0.7217	pathogenic	-0.99	Destabilizing	0.991	D	0.452	neutral	None	None	None	None	N
V/D	0.404	ambiguous	0.3413	ambiguous	-0.874	Destabilizing	0.801	D	0.559	neutral	N	0.490463026	None	None	N
V/E	0.3035	likely_benign	0.2806	benign	-0.876	Destabilizing	0.842	D	0.527	neutral	None	None	None	None	N
V/F	0.1539	likely_benign	0.137	benign	-0.957	Destabilizing	0.934	D	0.483	neutral	N	0.494708491	None	None	N
V/G	0.2868	likely_benign	0.2559	benign	-1.615	Destabilizing	0.625	D	0.559	neutral	N	0.49896564	None	None	N
V/H	0.4898	ambiguous	0.4503	ambiguous	-1.091	Destabilizing	0.998	D	0.539	neutral	None	None	None	None	N
V/I	0.0731	likely_benign	0.0674	benign	-0.576	Destabilizing	0.012	N	0.159	neutral	N	0.418084727	None	None	N
V/K	0.3314	likely_benign	0.3189	benign	-1.026	Destabilizing	0.842	D	0.545	neutral	None	None	None	None	N
V/L	0.162	likely_benign	0.1405	benign	-0.576	Destabilizing	0.454	N	0.346	neutral	N	0.482950403	None	None	N
V/M	0.1227	likely_benign	0.1121	benign	-0.523	Destabilizing	0.949	D	0.423	neutral	None	None	None	None	N
V/N	0.2616	likely_benign	0.209	benign	-0.837	Destabilizing	0.949	D	0.567	neutral	None	None	None	None	N
V/P	0.8832	likely_pathogenic	0.8564	pathogenic	-0.784	Destabilizing	0.974	D	0.534	neutral	None	None	None	None	N
V/Q	0.2965	likely_benign	0.2812	benign	-0.997	Destabilizing	0.974	D	0.541	neutral	None	None	None	None	N
V/R	0.3043	likely_benign	0.2938	benign	-0.552	Destabilizing	0.974	D	0.576	neutral	None	None	None	None	N
V/S	0.2106	likely_benign	0.1758	benign	-1.412	Destabilizing	0.08	N	0.22	neutral	None	None	None	None	N
V/T	0.1529	likely_benign	0.1368	benign	-1.303	Destabilizing	0.067	N	0.125	neutral	None	None	None	None	N
V/W	0.7992	likely_pathogenic	0.7758	pathogenic	-1.109	Destabilizing	0.998	D	0.603	neutral	None	None	None	None	N
V/Y	0.5152	ambiguous	0.4813	ambiguous	-0.814	Destabilizing	0.991	D	0.478	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.