TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25287	76084;76085;76086	chr2:178570273;178570272;178570271	chr2:179435000;179434999;179434998
N2AB	23646	71161;71162;71163	chr2:178570273;178570272;178570271	chr2:179435000;179434999;179434998
N2A	22719	68380;68381;68382	chr2:178570273;178570272;178570271	chr2:179435000;179434999;179434998
N2B	16222	48889;48890;48891	chr2:178570273;178570272;178570271	chr2:179435000;179434999;179434998
Novex-1	16347	49264;49265;49266	chr2:178570273;178570272;178570271	chr2:179435000;179434999;179434998
Novex-2	16414	49465;49466;49467	chr2:178570273;178570272;178570271	chr2:179435000;179434999;179434998
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: Fn3-71
• Domain position: 84
• Structural Position: 117
• Q(SASA): 0.3035
• 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	0.016	N	0.267	0.033	0.28722502521	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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	0.1324	likely_benign	0.1436	benign	-1.189	Destabilizing	0.201	N	0.519	neutral	N	0.480019201	None	None	I
V/C	0.6525	likely_pathogenic	0.708	pathogenic	-0.939	Destabilizing	0.992	D	0.577	neutral	None	None	None	None	I
V/D	0.4761	ambiguous	0.4704	ambiguous	-0.728	Destabilizing	0.009	N	0.526	neutral	N	0.503088062	None	None	I
V/E	0.3451	ambiguous	0.3417	ambiguous	-0.783	Destabilizing	0.447	N	0.654	neutral	None	None	None	None	I
V/F	0.1961	likely_benign	0.213	benign	-1.059	Destabilizing	0.81	D	0.605	neutral	N	0.480990343	None	None	I
V/G	0.2757	likely_benign	0.2835	benign	-1.432	Destabilizing	0.549	D	0.657	neutral	D	0.522596542	None	None	I
V/H	0.6062	likely_pathogenic	0.6394	pathogenic	-0.831	Destabilizing	0.992	D	0.665	neutral	None	None	None	None	I
V/I	0.0692	likely_benign	0.0719	benign	-0.655	Destabilizing	0.016	N	0.267	neutral	N	0.431977325	None	None	I
V/K	0.3564	ambiguous	0.3829	ambiguous	-0.876	Destabilizing	0.85	D	0.66	neutral	None	None	None	None	I
V/L	0.2111	likely_benign	0.2379	benign	-0.655	Destabilizing	0.08	N	0.492	neutral	N	0.486675815	None	None	I
V/M	0.15	likely_benign	0.1631	benign	-0.559	Destabilizing	0.103	N	0.479	neutral	None	None	None	None	I
V/N	0.3457	ambiguous	0.3735	ambiguous	-0.631	Destabilizing	0.739	D	0.672	neutral	None	None	None	None	I
V/P	0.3384	likely_benign	0.3895	ambiguous	-0.797	Destabilizing	0.92	D	0.67	neutral	None	None	None	None	I
V/Q	0.343	ambiguous	0.364	ambiguous	-0.871	Destabilizing	0.92	D	0.671	neutral	None	None	None	None	I
V/R	0.3034	likely_benign	0.3261	benign	-0.297	Destabilizing	0.85	D	0.677	prob.neutral	None	None	None	None	I
V/S	0.218	likely_benign	0.2314	benign	-1.149	Destabilizing	0.447	N	0.635	neutral	None	None	None	None	I
V/T	0.1297	likely_benign	0.1399	benign	-1.094	Destabilizing	0.005	N	0.23	neutral	None	None	None	None	I
V/W	0.798	likely_pathogenic	0.8238	pathogenic	-1.118	Destabilizing	0.992	D	0.706	prob.neutral	None	None	None	None	I
V/Y	0.5501	ambiguous	0.5983	pathogenic	-0.846	Destabilizing	0.92	D	0.593	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.