TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29108	87547;87548;87549	chr2:178558032;178558031;178558030	chr2:179422759;179422758;179422757
N2AB	27467	82624;82625;82626	chr2:178558032;178558031;178558030	chr2:179422759;179422758;179422757
N2A	26540	79843;79844;79845	chr2:178558032;178558031;178558030	chr2:179422759;179422758;179422757
N2B	20043	60352;60353;60354	chr2:178558032;178558031;178558030	chr2:179422759;179422758;179422757
Novex-1	20168	60727;60728;60729	chr2:178558032;178558031;178558030	chr2:179422759;179422758;179422757
Novex-2	20235	60928;60929;60930	chr2:178558032;178558031;178558030	chr2:179422759;179422758;179422757
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-145
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.2839
• 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	rs1393606181	-0.339	0.014	N	0.201	0.055	0.314716216878	gnomAD-2.1.1	8.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
V/I	rs1393606181	-0.339	0.014	N	0.201	0.055	0.314716216878	gnomAD-4.0.0	1.59103E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43271E-05	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	0.1568	likely_benign	0.1451	benign	-0.842	Destabilizing	0.822	D	0.437	neutral	N	0.490516701	None	None	I
V/C	0.5963	likely_pathogenic	0.5625	ambiguous	-0.691	Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	I
V/D	0.3313	likely_benign	0.2995	benign	-0.428	Destabilizing	0.99	D	0.815	deleterious	N	0.484764165	None	None	I
V/E	0.2866	likely_benign	0.2716	benign	-0.53	Destabilizing	0.993	D	0.77	deleterious	None	None	None	None	I
V/F	0.1631	likely_benign	0.1512	benign	-1.007	Destabilizing	0.942	D	0.758	deleterious	N	0.510142612	None	None	I
V/G	0.184	likely_benign	0.1824	benign	-1.016	Destabilizing	0.971	D	0.785	deleterious	N	0.48033978	None	None	I
V/H	0.4741	ambiguous	0.4318	ambiguous	-0.549	Destabilizing	0.998	D	0.816	deleterious	None	None	None	None	I
V/I	0.073	likely_benign	0.07	benign	-0.522	Destabilizing	0.014	N	0.201	neutral	N	0.499714975	None	None	I
V/K	0.3115	likely_benign	0.289	benign	-0.57	Destabilizing	0.978	D	0.781	deleterious	None	None	None	None	I
V/L	0.1365	likely_benign	0.121	benign	-0.522	Destabilizing	0.247	N	0.431	neutral	N	0.476646114	None	None	I
V/M	0.095	likely_benign	0.0899	benign	-0.328	Destabilizing	0.956	D	0.777	deleterious	None	None	None	None	I
V/N	0.1827	likely_benign	0.1573	benign	-0.294	Destabilizing	0.993	D	0.819	deleterious	None	None	None	None	I
V/P	0.8213	likely_pathogenic	0.7708	pathogenic	-0.593	Destabilizing	0.993	D	0.805	deleterious	None	None	None	None	I
V/Q	0.255	likely_benign	0.2421	benign	-0.575	Destabilizing	0.993	D	0.809	deleterious	None	None	None	None	I
V/R	0.297	likely_benign	0.2734	benign	-0.02	Destabilizing	0.993	D	0.821	deleterious	None	None	None	None	I
V/S	0.1589	likely_benign	0.1449	benign	-0.746	Destabilizing	0.978	D	0.765	deleterious	None	None	None	None	I
V/T	0.1331	likely_benign	0.1202	benign	-0.746	Destabilizing	0.86	D	0.642	neutral	None	None	None	None	I
V/W	0.7887	likely_pathogenic	0.7776	pathogenic	-1.061	Destabilizing	0.998	D	0.835	deleterious	None	None	None	None	I
V/Y	0.5062	ambiguous	0.4699	ambiguous	-0.758	Destabilizing	0.978	D	0.784	deleterious	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.