TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8739	26440;26441;26442	chr2:178714559;178714558;178714557	chr2:179579286;179579285;179579284
N2AB	8422	25489;25490;25491	chr2:178714559;178714558;178714557	chr2:179579286;179579285;179579284
N2A	7495	22708;22709;22710	chr2:178714559;178714558;178714557	chr2:179579286;179579285;179579284
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-73
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.484
• 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	None	None	None	N	0.119	0.073	0.226586394389	gnomAD-4.0.0	1.61987E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.07012E-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	0.1285	likely_benign	0.1701	benign	-0.968	Destabilizing	0.045	N	0.43	neutral	N	0.475797832	None	None	N
V/C	0.6283	likely_pathogenic	0.7171	pathogenic	-0.767	Destabilizing	0.961	D	0.535	neutral	None	None	None	None	N
V/D	0.2757	likely_benign	0.3831	ambiguous	-0.444	Destabilizing	0.723	D	0.644	neutral	None	None	None	None	N
V/E	0.182	likely_benign	0.2341	benign	-0.509	Destabilizing	0.242	N	0.542	neutral	N	0.473088807	None	None	N
V/F	0.1249	likely_benign	0.1671	benign	-0.819	Destabilizing	0.496	N	0.506	neutral	None	None	None	None	N
V/G	0.1372	likely_benign	0.1852	benign	-1.192	Destabilizing	0.727	D	0.549	neutral	N	0.503563326	None	None	N
V/H	0.3588	ambiguous	0.4425	ambiguous	-0.587	Destabilizing	0.97	D	0.663	neutral	None	None	None	None	N
V/I	0.0721	likely_benign	0.0762	benign	-0.495	Destabilizing	0.01	N	0.421	neutral	None	None	None	None	N
V/K	0.1815	likely_benign	0.2272	benign	-0.785	Destabilizing	0.479	N	0.543	neutral	None	None	None	None	N
V/L	0.1135	likely_benign	0.1453	benign	-0.495	Destabilizing	None	N	0.119	neutral	N	0.480314698	None	None	N
V/M	0.1195	likely_benign	0.1482	benign	-0.428	Destabilizing	0.347	N	0.481	neutral	N	0.466847837	None	None	N
V/N	0.2057	likely_benign	0.2736	benign	-0.526	Destabilizing	0.12	N	0.647	neutral	None	None	None	None	N
V/P	0.5282	ambiguous	0.7144	pathogenic	-0.617	Destabilizing	0.458	N	0.611	neutral	None	None	None	None	N
V/Q	0.1768	likely_benign	0.2078	benign	-0.751	Destabilizing	0.57	D	0.602	neutral	None	None	None	None	N
V/R	0.1497	likely_benign	0.1872	benign	-0.218	Destabilizing	0.799	D	0.637	neutral	None	None	None	None	N
V/S	0.1379	likely_benign	0.1838	benign	-1.029	Destabilizing	0.027	N	0.275	neutral	None	None	None	None	N
V/T	0.1299	likely_benign	0.1659	benign	-0.989	Destabilizing	0.109	N	0.384	neutral	None	None	None	None	N
V/W	0.6069	likely_pathogenic	0.74	pathogenic	-0.892	Destabilizing	0.992	D	0.711	prob.delet.	None	None	None	None	N
V/Y	0.3995	ambiguous	0.5027	ambiguous	-0.626	Destabilizing	0.799	D	0.495	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.