TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31028	93307;93308;93309	chr2:178548544;178548543;178548542	chr2:179413271;179413270;179413269
N2AB	29387	88384;88385;88386	chr2:178548544;178548543;178548542	chr2:179413271;179413270;179413269
N2A	28460	85603;85604;85605	chr2:178548544;178548543;178548542	chr2:179413271;179413270;179413269
N2B	21963	66112;66113;66114	chr2:178548544;178548543;178548542	chr2:179413271;179413270;179413269
Novex-1	22088	66487;66488;66489	chr2:178548544;178548543;178548542	chr2:179413271;179413270;179413269
Novex-2	22155	66688;66689;66690	chr2:178548544;178548543;178548542	chr2:179413271;179413270;179413269
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: Fn3-114
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.2268
• 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/M	None	None	0.999	N	0.599	0.446	0.650362002609	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	0.4844	ambiguous	0.4386	ambiguous	-0.555	Destabilizing	0.989	D	0.465	neutral	N	0.47063845	None	None	N
V/C	0.8605	likely_pathogenic	0.8471	pathogenic	-0.775	Destabilizing	1.0	D	0.66	neutral	None	None	None	None	N
V/D	0.8918	likely_pathogenic	0.8736	pathogenic	-0.15	Destabilizing	0.995	D	0.683	prob.neutral	None	None	None	None	N
V/E	0.8164	likely_pathogenic	0.7813	pathogenic	-0.239	Destabilizing	0.733	D	0.358	neutral	N	0.517963003	None	None	N
V/F	0.4449	ambiguous	0.4496	ambiguous	-0.93	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
V/G	0.6054	likely_pathogenic	0.5614	ambiguous	-0.695	Destabilizing	0.998	D	0.685	prob.neutral	N	0.51948394	None	None	N
V/H	0.9217	likely_pathogenic	0.9065	pathogenic	-0.433	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
V/I	0.0786	likely_benign	0.0772	benign	-0.325	Destabilizing	0.997	D	0.482	neutral	None	None	None	None	N
V/K	0.7997	likely_pathogenic	0.7486	pathogenic	-0.189	Destabilizing	0.998	D	0.615	neutral	None	None	None	None	N
V/L	0.4505	ambiguous	0.415	ambiguous	-0.325	Destabilizing	0.987	D	0.481	neutral	N	0.51934838	None	None	N
V/M	0.2622	likely_benign	0.2496	benign	-0.287	Destabilizing	0.999	D	0.599	neutral	N	0.509760249	None	None	N
V/N	0.756	likely_pathogenic	0.7212	pathogenic	-0.002	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
V/P	0.9322	likely_pathogenic	0.9159	pathogenic	-0.369	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
V/Q	0.7922	likely_pathogenic	0.7447	pathogenic	-0.26	Destabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	N
V/R	0.7613	likely_pathogenic	0.6948	pathogenic	0.171	Stabilizing	0.998	D	0.764	deleterious	None	None	None	None	N
V/S	0.6512	likely_pathogenic	0.6037	pathogenic	-0.447	Destabilizing	0.998	D	0.611	neutral	None	None	None	None	N
V/T	0.4334	ambiguous	0.3957	ambiguous	-0.435	Destabilizing	0.996	D	0.477	neutral	None	None	None	None	N
V/W	0.9646	likely_pathogenic	0.9632	pathogenic	-0.995	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
V/Y	0.8724	likely_pathogenic	0.8524	pathogenic	-0.615	Destabilizing	1.0	D	0.704	prob.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.