TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19800	59623;59624;59625	chr2:178592607;178592606;178592605	chr2:179457334;179457333;179457332
N2AB	18159	54700;54701;54702	chr2:178592607;178592606;178592605	chr2:179457334;179457333;179457332
N2A	17232	51919;51920;51921	chr2:178592607;178592606;178592605	chr2:179457334;179457333;179457332
N2B	10735	32428;32429;32430	chr2:178592607;178592606;178592605	chr2:179457334;179457333;179457332
Novex-1	10860	32803;32804;32805	chr2:178592607;178592606;178592605	chr2:179457334;179457333;179457332
Novex-2	10927	33004;33005;33006	chr2:178592607;178592606;178592605	chr2:179457334;179457333;179457332
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-119
• Domain position: 11
• Structural Position: 23
• Q(SASA): 0.4752
• 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/A	rs747359962	None	0.002	N	0.111	0.131	0.247322355667	gnomAD-4.0.0	1.02654E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.34938E-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	0.0762	likely_benign	0.0674	benign	-1.051	Destabilizing	0.002	N	0.111	neutral	N	0.358084494	None	None	N
V/C	0.69	likely_pathogenic	0.6656	pathogenic	-0.743	Destabilizing	0.974	D	0.325	neutral	None	None	None	None	N
V/D	0.3607	ambiguous	0.3513	ambiguous	-0.743	Destabilizing	0.966	D	0.417	neutral	N	0.482800429	None	None	N
V/E	0.2429	likely_benign	0.2272	benign	-0.817	Destabilizing	0.842	D	0.385	neutral	None	None	None	None	N
V/F	0.2701	likely_benign	0.2495	benign	-1.006	Destabilizing	0.966	D	0.365	neutral	N	0.512429903	None	None	N
V/G	0.2031	likely_benign	0.1918	benign	-1.277	Destabilizing	0.454	N	0.361	neutral	N	0.49886596	None	None	N
V/H	0.5488	ambiguous	0.5246	ambiguous	-0.774	Destabilizing	0.998	D	0.397	neutral	None	None	None	None	N
V/I	0.0994	likely_benign	0.0872	benign	-0.574	Destabilizing	0.625	D	0.365	neutral	N	0.471794002	None	None	N
V/K	0.2663	likely_benign	0.2458	benign	-0.864	Destabilizing	0.842	D	0.405	neutral	None	None	None	None	N
V/L	0.2837	likely_benign	0.2467	benign	-0.574	Destabilizing	0.625	D	0.316	neutral	N	0.459518138	None	None	N
V/M	0.1683	likely_benign	0.1416	benign	-0.41	Destabilizing	0.991	D	0.337	neutral	None	None	None	None	N
V/N	0.2629	likely_benign	0.2313	benign	-0.561	Destabilizing	0.974	D	0.433	neutral	None	None	None	None	N
V/P	0.5465	ambiguous	0.5238	ambiguous	-0.697	Destabilizing	0.974	D	0.404	neutral	None	None	None	None	N
V/Q	0.2806	likely_benign	0.2576	benign	-0.813	Destabilizing	0.974	D	0.411	neutral	None	None	None	None	N
V/R	0.2441	likely_benign	0.2413	benign	-0.275	Destabilizing	0.974	D	0.421	neutral	None	None	None	None	N
V/S	0.1523	likely_benign	0.1297	benign	-1.017	Destabilizing	0.525	D	0.325	neutral	None	None	None	None	N
V/T	0.1286	likely_benign	0.1078	benign	-0.988	Destabilizing	0.688	D	0.28	neutral	None	None	None	None	N
V/W	0.8494	likely_pathogenic	0.8424	pathogenic	-1.098	Destabilizing	0.998	D	0.474	neutral	None	None	None	None	N
V/Y	0.5927	likely_pathogenic	0.5712	pathogenic	-0.822	Destabilizing	0.991	D	0.348	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.