TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9667	29224;29225;29226	chr2:178707568;178707567;178707566	chr2:179572295;179572294;179572293
N2AB	9350	28273;28274;28275	chr2:178707568;178707567;178707566	chr2:179572295;179572294;179572293
N2A	8423	25492;25493;25494	chr2:178707568;178707567;178707566	chr2:179572295;179572294;179572293
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: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-82
• Domain position: 78
• Structural Position: 162
• Q(SASA): 0.9745
• 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/M	None	None	0.001	None	0.202	0.055	0.288727942641	gnomAD-4.0.0	1.59144E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43316E-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	0.1469	likely_benign	0.0888	benign	-0.393	Destabilizing	None	N	0.075	neutral	None	None	None	None	I
V/C	0.8315	likely_pathogenic	0.7315	pathogenic	-0.884	Destabilizing	0.245	N	0.227	neutral	None	None	None	None	I
V/D	0.3616	ambiguous	0.2304	benign	-0.368	Destabilizing	None	N	0.123	neutral	None	None	None	None	I
V/E	0.2808	likely_benign	0.1905	benign	-0.483	Destabilizing	None	N	0.097	neutral	None	None	None	None	I
V/F	0.2346	likely_benign	0.1501	benign	-0.784	Destabilizing	0.044	N	0.245	neutral	None	None	None	None	I
V/G	0.2299	likely_benign	0.1398	benign	-0.434	Destabilizing	None	N	0.123	neutral	None	None	None	None	I
V/H	0.6261	likely_pathogenic	0.4666	ambiguous	-0.061	Destabilizing	0.497	N	0.21	neutral	None	None	None	None	I
V/I	0.0873	likely_benign	0.0779	benign	-0.419	Destabilizing	0.009	N	0.223	neutral	None	None	None	None	I
V/K	0.3867	ambiguous	0.267	benign	-0.417	Destabilizing	0.018	N	0.216	neutral	None	None	None	None	I
V/L	0.2065	likely_benign	0.1392	benign	-0.419	Destabilizing	None	N	0.114	neutral	None	None	None	None	I
V/M	0.1411	likely_benign	0.0898	benign	-0.623	Destabilizing	0.001	N	0.202	neutral	None	None	None	None	I
V/N	0.287	likely_benign	0.1843	benign	-0.247	Destabilizing	0.018	N	0.293	neutral	None	None	None	None	I
V/P	0.4765	ambiguous	0.3215	benign	-0.385	Destabilizing	0.044	N	0.327	neutral	None	None	None	None	I
V/Q	0.3275	likely_benign	0.2334	benign	-0.45	Destabilizing	0.044	N	0.341	neutral	None	None	None	None	I
V/R	0.3754	ambiguous	0.2491	benign	0.013	Stabilizing	0.044	N	0.31	neutral	None	None	None	None	I
V/S	0.1865	likely_benign	0.1217	benign	-0.557	Destabilizing	None	N	0.115	neutral	None	None	None	None	I
V/T	0.1513	likely_benign	0.1107	benign	-0.585	Destabilizing	0.009	N	0.161	neutral	None	None	None	None	I
V/W	0.8243	likely_pathogenic	0.7208	pathogenic	-0.824	Destabilizing	0.788	D	0.203	neutral	None	None	None	None	I
V/Y	0.6204	likely_pathogenic	0.4969	ambiguous	-0.569	Destabilizing	0.245	N	0.254	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.