TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7191	21796;21797;21798	chr2:178723529;178723528;178723527	chr2:179588256;179588255;179588254
N2AB	6874	20845;20846;20847	chr2:178723529;178723528;178723527	chr2:179588256;179588255;179588254
N2A	5947	18064;18065;18066	chr2:178723529;178723528;178723527	chr2:179588256;179588255;179588254
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-56
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.2469
• 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	rs1338451033	None	0.934	D	0.497	0.274	0.389439708392	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/M	rs1338451033	None	0.934	D	0.497	0.274	0.389439708392	gnomAD-4.0.0	6.57246E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.4702E-05	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	0.147	likely_benign	0.1431	benign	-1.497	Destabilizing	0.022	N	0.12	neutral	N	0.488299676	None	None	N
V/C	0.8088	likely_pathogenic	0.8031	pathogenic	-0.959	Destabilizing	0.998	D	0.519	neutral	None	None	None	None	N
V/D	0.3558	ambiguous	0.341	ambiguous	-1.324	Destabilizing	0.842	D	0.603	neutral	None	None	None	None	N
V/E	0.2226	likely_benign	0.2118	benign	-1.304	Destabilizing	0.801	D	0.543	neutral	N	0.520338176	None	None	N
V/F	0.1406	likely_benign	0.1368	benign	-1.123	Destabilizing	0.949	D	0.549	neutral	None	None	None	None	N
V/G	0.2839	likely_benign	0.2695	benign	-1.839	Destabilizing	0.669	D	0.569	neutral	N	0.504024716	None	None	N
V/H	0.4783	ambiguous	0.4596	ambiguous	-1.434	Destabilizing	0.998	D	0.593	neutral	None	None	None	None	N
V/I	0.0774	likely_benign	0.0798	benign	-0.648	Destabilizing	0.016	N	0.169	neutral	None	None	None	None	N
V/K	0.2635	likely_benign	0.2447	benign	-1.138	Destabilizing	0.728	D	0.559	neutral	None	None	None	None	N
V/L	0.1884	likely_benign	0.1904	benign	-0.648	Destabilizing	0.454	N	0.416	neutral	N	0.512201482	None	None	N
V/M	0.1072	likely_benign	0.1086	benign	-0.491	Destabilizing	0.934	D	0.497	neutral	D	0.523938629	None	None	N
V/N	0.2957	likely_benign	0.2867	benign	-0.95	Destabilizing	0.949	D	0.609	neutral	None	None	None	None	N
V/P	0.8534	likely_pathogenic	0.8362	pathogenic	-0.897	Destabilizing	0.974	D	0.581	neutral	None	None	None	None	N
V/Q	0.2884	likely_benign	0.2703	benign	-1.097	Destabilizing	0.949	D	0.589	neutral	None	None	None	None	N
V/R	0.2443	likely_benign	0.2237	benign	-0.691	Destabilizing	0.016	N	0.498	neutral	None	None	None	None	N
V/S	0.2099	likely_benign	0.2057	benign	-1.509	Destabilizing	0.08	N	0.309	neutral	None	None	None	None	N
V/T	0.1426	likely_benign	0.1398	benign	-1.379	Destabilizing	0.525	D	0.442	neutral	None	None	None	None	N
V/W	0.7425	likely_pathogenic	0.7256	pathogenic	-1.358	Destabilizing	0.998	D	0.646	neutral	None	None	None	None	N
V/Y	0.5051	ambiguous	0.4843	ambiguous	-1.045	Destabilizing	0.991	D	0.537	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.