TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32593	98002;98003;98004	chr2:178541300;178541299;178541298	chr2:179406027;179406026;179406025
N2AB	30952	93079;93080;93081	chr2:178541300;178541299;178541298	chr2:179406027;179406026;179406025
N2A	30025	90298;90299;90300	chr2:178541300;178541299;178541298	chr2:179406027;179406026;179406025
N2B	23528	70807;70808;70809	chr2:178541300;178541299;178541298	chr2:179406027;179406026;179406025
Novex-1	23653	71182;71183;71184	chr2:178541300;178541299;178541298	chr2:179406027;179406026;179406025
Novex-2	23720	71383;71384;71385	chr2:178541300;178541299;178541298	chr2:179406027;179406026;179406025
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: Fn3-125
• Domain position: 95
• Structural Position: 129
• Q(SASA): 0.3323
• 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	rs763858575	-0.214	0.036	N	0.249	0.067	0.436455679973	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
V/I	rs763858575	-0.214	0.036	N	0.249	0.067	0.436455679973	gnomAD-4.0.0	1.1885E-05	None	None	None	None	I	None	0	2.01711E-05	None	0	0	None	0	0	1.42592E-05	0	1.70952E-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	0.1654	likely_benign	0.1782	benign	-1.146	Destabilizing	0.682	D	0.468	neutral	N	0.4902287	None	None	I
V/C	0.6866	likely_pathogenic	0.6796	pathogenic	-0.735	Destabilizing	0.996	D	0.768	deleterious	None	None	None	None	I
V/D	0.5858	likely_pathogenic	0.6077	pathogenic	-1.028	Destabilizing	0.979	D	0.799	deleterious	N	0.484642826	None	None	I
V/E	0.4015	ambiguous	0.4253	ambiguous	-1.072	Destabilizing	0.984	D	0.749	deleterious	None	None	None	None	I
V/F	0.1744	likely_benign	0.1778	benign	-0.981	Destabilizing	0.95	D	0.757	deleterious	N	0.507814383	None	None	I
V/G	0.3221	likely_benign	0.3525	ambiguous	-1.406	Destabilizing	0.938	D	0.763	deleterious	N	0.513342918	None	None	I
V/H	0.5841	likely_pathogenic	0.5919	pathogenic	-0.882	Destabilizing	0.996	D	0.773	deleterious	None	None	None	None	I
V/I	0.0808	likely_benign	0.0772	benign	-0.56	Destabilizing	0.036	N	0.249	neutral	N	0.489535267	None	None	I
V/K	0.3236	likely_benign	0.3552	ambiguous	-1.003	Destabilizing	0.953	D	0.748	deleterious	None	None	None	None	I
V/L	0.1615	likely_benign	0.1536	benign	-0.56	Destabilizing	0.279	N	0.516	neutral	N	0.487092394	None	None	I
V/M	0.135	likely_benign	0.1368	benign	-0.418	Destabilizing	0.909	D	0.702	prob.delet.	None	None	None	None	I
V/N	0.4372	ambiguous	0.4299	ambiguous	-0.746	Destabilizing	0.984	D	0.801	deleterious	None	None	None	None	I
V/P	0.4483	ambiguous	0.4507	ambiguous	-0.72	Destabilizing	0.984	D	0.787	deleterious	None	None	None	None	I
V/Q	0.3381	likely_benign	0.3513	ambiguous	-0.965	Destabilizing	0.984	D	0.769	deleterious	None	None	None	None	I
V/R	0.2482	likely_benign	0.2848	benign	-0.402	Destabilizing	0.984	D	0.788	deleterious	None	None	None	None	I
V/S	0.2792	likely_benign	0.2833	benign	-1.182	Destabilizing	0.953	D	0.709	prob.delet.	None	None	None	None	I
V/T	0.1501	likely_benign	0.1549	benign	-1.122	Destabilizing	0.74	D	0.631	neutral	None	None	None	None	I
V/W	0.7515	likely_pathogenic	0.7677	pathogenic	-1.127	Destabilizing	0.996	D	0.715	prob.delet.	None	None	None	None	I
V/Y	0.5322	ambiguous	0.5268	ambiguous	-0.844	Destabilizing	0.953	D	0.781	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.