TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5350	16273;16274;16275	chr2:178733245;178733244;178733243	chr2:179597972;179597971;179597970
N2AB	5033	15322;15323;15324	chr2:178733245;178733244;178733243	chr2:179597972;179597971;179597970
N2A	4106	12541;12542;12543	chr2:178733245;178733244;178733243	chr2:179597972;179597971;179597970
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: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-36
• Domain position: 90
• Structural Position: 176
• Q(SASA): 0.263
• 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	rs2080869284	None	0.767	N	0.553	0.392	0.656978821447	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.54E-05	0	0	0	None	0	0	0	0	0
V/I	rs2080869284	None	0.767	N	0.553	0.392	0.656978821447	gnomAD-4.0.0	2.62072E-06	None	None	None	None	N	None	0	1.72909E-05	None	0	0	None	0	0	0	1.41355E-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	0.9217	likely_pathogenic	0.8977	pathogenic	-1.787	Destabilizing	0.998	D	0.723	prob.delet.	D	0.63523419	None	None	N
V/C	0.9898	likely_pathogenic	0.9892	pathogenic	-1.535	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
V/D	0.9982	likely_pathogenic	0.9983	pathogenic	-1.888	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
V/E	0.9936	likely_pathogenic	0.9935	pathogenic	-1.788	Destabilizing	1.0	D	0.852	deleterious	D	0.635839603	None	None	N
V/F	0.953	likely_pathogenic	0.9546	pathogenic	-1.246	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/G	0.9695	likely_pathogenic	0.9659	pathogenic	-2.186	Highly Destabilizing	1.0	D	0.841	deleterious	D	0.635839603	None	None	N
V/H	0.9985	likely_pathogenic	0.9985	pathogenic	-1.729	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
V/I	0.1325	likely_benign	0.1238	benign	-0.738	Destabilizing	0.767	D	0.553	neutral	N	0.508548704	None	None	N
V/K	0.9958	likely_pathogenic	0.9959	pathogenic	-1.261	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
V/L	0.8214	likely_pathogenic	0.7956	pathogenic	-0.738	Destabilizing	0.981	D	0.728	prob.delet.	D	0.607678036	None	None	N
V/M	0.843	likely_pathogenic	0.8224	pathogenic	-0.86	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/N	0.9917	likely_pathogenic	0.9916	pathogenic	-1.307	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/P	0.9892	likely_pathogenic	0.9889	pathogenic	-1.058	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/Q	0.994	likely_pathogenic	0.9941	pathogenic	-1.365	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/R	0.9919	likely_pathogenic	0.992	pathogenic	-0.958	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/S	0.9722	likely_pathogenic	0.9683	pathogenic	-1.938	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
V/T	0.9395	likely_pathogenic	0.9283	pathogenic	-1.717	Destabilizing	0.998	D	0.81	deleterious	None	None	None	None	N
V/W	0.9995	likely_pathogenic	0.9995	pathogenic	-1.521	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
V/Y	0.9963	likely_pathogenic	0.9967	pathogenic	-1.178	Destabilizing	1.0	D	0.855	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.