TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26871	80836;80837;80838	chr2:178565521;178565520;178565519	chr2:179430248;179430247;179430246
N2AB	25230	75913;75914;75915	chr2:178565521;178565520;178565519	chr2:179430248;179430247;179430246
N2A	24303	73132;73133;73134	chr2:178565521;178565520;178565519	chr2:179430248;179430247;179430246
N2B	17806	53641;53642;53643	chr2:178565521;178565520;178565519	chr2:179430248;179430247;179430246
Novex-1	17931	54016;54017;54018	chr2:178565521;178565520;178565519	chr2:179430248;179430247;179430246
Novex-2	17998	54217;54218;54219	chr2:178565521;178565520;178565519	chr2:179430248;179430247;179430246
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-83
• Domain position: 92
• Structural Position: 127
• Q(SASA): 0.2063
• 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/I	None	None	0.984	N	0.547	0.272	0.543691374674	gnomAD-4.0.0	2.05302E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99603E-07	0	3.31422E-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	0.6996	likely_pathogenic	0.6757	pathogenic	-1.721	Destabilizing	0.999	D	0.627	neutral	N	0.508237129	None	None	N
V/C	0.9378	likely_pathogenic	0.9345	pathogenic	-1.057	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
V/D	0.9925	likely_pathogenic	0.9919	pathogenic	-2.505	Highly Destabilizing	1.0	D	0.905	deleterious	D	0.532724166	None	None	N
V/E	0.9706	likely_pathogenic	0.9667	pathogenic	-2.239	Highly Destabilizing	0.999	D	0.89	deleterious	None	None	None	None	N
V/F	0.6548	likely_pathogenic	0.6301	pathogenic	-1.058	Destabilizing	1.0	D	0.825	deleterious	D	0.532977656	None	None	N
V/G	0.8736	likely_pathogenic	0.8681	pathogenic	-2.249	Highly Destabilizing	1.0	D	0.896	deleterious	D	0.532977656	None	None	N
V/H	0.9894	likely_pathogenic	0.9873	pathogenic	-2.002	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
V/I	0.1048	likely_benign	0.1019	benign	-0.224	Destabilizing	0.984	D	0.547	neutral	N	0.498077392	None	None	N
V/K	0.9787	likely_pathogenic	0.9757	pathogenic	-1.438	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
V/L	0.5823	likely_pathogenic	0.5358	ambiguous	-0.224	Destabilizing	0.984	D	0.611	neutral	N	0.50123569	None	None	N
V/M	0.4964	ambiguous	0.4513	ambiguous	-0.246	Destabilizing	1.0	D	0.662	prob.neutral	None	None	None	None	N
V/N	0.9741	likely_pathogenic	0.9703	pathogenic	-1.972	Destabilizing	0.998	D	0.912	deleterious	None	None	None	None	N
V/P	0.989	likely_pathogenic	0.9909	pathogenic	-0.701	Destabilizing	0.998	D	0.887	deleterious	None	None	None	None	N
V/Q	0.9624	likely_pathogenic	0.9549	pathogenic	-1.719	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
V/R	0.9668	likely_pathogenic	0.9614	pathogenic	-1.481	Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
V/S	0.9001	likely_pathogenic	0.8879	pathogenic	-2.497	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
V/T	0.7478	likely_pathogenic	0.723	pathogenic	-2.076	Highly Destabilizing	0.998	D	0.525	neutral	None	None	None	None	N
V/W	0.9935	likely_pathogenic	0.9916	pathogenic	-1.564	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
V/Y	0.9632	likely_pathogenic	0.9582	pathogenic	-1.11	Destabilizing	1.0	D	0.812	deleterious	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.