TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6304	19135;19136;19137	chr2:178729128;178729127;178729126	chr2:179593855;179593854;179593853
N2AB	5987	18184;18185;18186	chr2:178729128;178729127;178729126	chr2:179593855;179593854;179593853
N2A	5060	15403;15404;15405	chr2:178729128;178729127;178729126	chr2:179593855;179593854;179593853
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-47
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.5678
• Predicted PPI site: I

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/I	None	None	0.117	N	0.309	0.08	0.427368086475	gnomAD-4.0.0	6.88716E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.02961E-07	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	0.2078	likely_benign	0.1842	benign	-0.683	Destabilizing	0.977	D	0.548	neutral	N	0.509006462	None	None	I
V/C	0.8232	likely_pathogenic	0.8025	pathogenic	-0.73	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	I
V/D	0.4389	ambiguous	0.3607	ambiguous	-0.101	Destabilizing	0.999	D	0.754	deleterious	D	0.527477579	None	None	I
V/E	0.2848	likely_benign	0.2516	benign	-0.181	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	I
V/F	0.1395	likely_benign	0.1293	benign	-0.672	Destabilizing	0.993	D	0.668	neutral	N	0.497809557	None	None	I
V/G	0.3038	likely_benign	0.2569	benign	-0.87	Destabilizing	0.999	D	0.727	prob.delet.	N	0.486426798	None	None	I
V/H	0.5893	likely_pathogenic	0.5514	ambiguous	-0.322	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
V/I	0.0734	likely_benign	0.0737	benign	-0.326	Destabilizing	0.117	N	0.309	neutral	N	0.490652774	None	None	I
V/K	0.3474	ambiguous	0.3184	benign	-0.522	Destabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	I
V/L	0.1407	likely_benign	0.1407	benign	-0.326	Destabilizing	0.898	D	0.559	neutral	N	0.455558766	None	None	I
V/M	0.1168	likely_benign	0.1142	benign	-0.37	Destabilizing	0.995	D	0.672	neutral	None	None	None	None	I
V/N	0.3087	likely_benign	0.2646	benign	-0.311	Destabilizing	0.999	D	0.754	deleterious	None	None	None	None	I
V/P	0.5377	ambiguous	0.5136	ambiguous	-0.408	Destabilizing	0.999	D	0.74	deleterious	None	None	None	None	I
V/Q	0.3199	likely_benign	0.2979	benign	-0.515	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	I
V/R	0.3183	likely_benign	0.3095	benign	-0.021	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	I
V/S	0.2502	likely_benign	0.2184	benign	-0.789	Destabilizing	0.998	D	0.725	prob.delet.	None	None	None	None	I
V/T	0.1968	likely_benign	0.177	benign	-0.76	Destabilizing	0.983	D	0.659	neutral	None	None	None	None	I
V/W	0.8076	likely_pathogenic	0.7843	pathogenic	-0.746	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
V/Y	0.521	ambiguous	0.4939	ambiguous	-0.455	Destabilizing	0.999	D	0.675	neutral	None	None	None	None	I

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.