TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7619	23080;23081;23082	chr2:178721164;178721163;178721162	chr2:179585891;179585890;179585889
N2AB	7302	22129;22130;22131	chr2:178721164;178721163;178721162	chr2:179585891;179585890;179585889
N2A	6375	19348;19349;19350	chr2:178721164;178721163;178721162	chr2:179585891;179585890;179585889
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-61
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.7258
• 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	rs770870073	0.103	0.007	N	0.193	0.137	0.176091768786	gnomAD-2.1.1	8.12E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
V/L	rs770870073	0.103	0.007	N	0.193	0.137	0.176091768786	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/L	rs770870073	0.103	0.007	N	0.193	0.137	0.176091768786	gnomAD-4.0.0	1.49484E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.8739E-05	0	3.2231E-05

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	0.1634	likely_benign	0.1532	benign	-0.6	Destabilizing	0.037	N	0.201	neutral	D	0.52769101	None	None	N
V/C	0.7642	likely_pathogenic	0.7673	pathogenic	-0.656	Destabilizing	0.859	D	0.299	neutral	None	None	None	None	N
V/D	0.3265	likely_benign	0.29	benign	-0.399	Destabilizing	0.301	N	0.418	neutral	D	0.532232825	None	None	N
V/E	0.2402	likely_benign	0.2334	benign	-0.504	Destabilizing	0.22	N	0.343	neutral	None	None	None	None	N
V/F	0.1249	likely_benign	0.1247	benign	-0.741	Destabilizing	None	N	0.141	neutral	D	0.530502029	None	None	N
V/G	0.2504	likely_benign	0.2261	benign	-0.759	Destabilizing	0.301	N	0.371	neutral	D	0.537966719	None	None	N
V/H	0.5116	ambiguous	0.4868	ambiguous	-0.308	Destabilizing	0.001	N	0.185	neutral	None	None	None	None	N
V/I	0.0676	likely_benign	0.0686	benign	-0.326	Destabilizing	None	N	0.103	neutral	N	0.498640326	None	None	N
V/K	0.4021	ambiguous	0.3831	ambiguous	-0.579	Destabilizing	0.004	N	0.188	neutral	None	None	None	None	N
V/L	0.1505	likely_benign	0.1453	benign	-0.326	Destabilizing	0.007	N	0.193	neutral	N	0.489308767	None	None	N
V/M	0.1192	likely_benign	0.1226	benign	-0.353	Destabilizing	0.025	N	0.2	neutral	None	None	None	None	N
V/N	0.2537	likely_benign	0.2201	benign	-0.296	Destabilizing	0.22	N	0.431	neutral	None	None	None	None	N
V/P	0.5732	likely_pathogenic	0.5795	pathogenic	-0.381	Destabilizing	0.001	N	0.215	neutral	None	None	None	None	N
V/Q	0.3246	likely_benign	0.304	benign	-0.542	Destabilizing	0.22	N	0.417	neutral	None	None	None	None	N
V/R	0.3571	ambiguous	0.3319	benign	-0.036	Destabilizing	0.124	N	0.448	neutral	None	None	None	None	N
V/S	0.2078	likely_benign	0.1832	benign	-0.676	Destabilizing	0.104	N	0.316	neutral	None	None	None	None	N
V/T	0.1385	likely_benign	0.1326	benign	-0.678	Destabilizing	0.104	N	0.207	neutral	None	None	None	None	N
V/W	0.6563	likely_pathogenic	0.6802	pathogenic	-0.824	Destabilizing	0.958	D	0.309	neutral	None	None	None	None	N
V/Y	0.4186	ambiguous	0.4183	ambiguous	-0.531	Destabilizing	0.124	N	0.352	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.