TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8227	24904;24905;24906	chr2:178718427;178718426;178718425	chr2:179583154;179583153;179583152
N2AB	7910	23953;23954;23955	chr2:178718427;178718426;178718425	chr2:179583154;179583153;179583152
N2A	6983	21172;21173;21174	chr2:178718427;178718426;178718425	chr2:179583154;179583153;179583152
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: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-67
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.2014
• Predicted PPI site: I

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
I/M	rs1300167182	-1.305	0.994	N	0.561	0.353	0.498513350342	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	2.67E-05	0
I/M	rs1300167182	-1.305	0.994	N	0.561	0.353	0.498513350342	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	2.94E-05	0	0
I/M	rs1300167182	-1.305	0.994	N	0.561	0.353	0.498513350342	gnomAD-4.0.0	8.67628E-06	None	None	None	None	I	None	0	1.667E-05	None	0	0	None	0	0	1.10194E-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
I/A	0.6743	likely_pathogenic	0.6869	pathogenic	-2.183	Highly Destabilizing	0.993	D	0.534	neutral	None	None	None	None	I
I/C	0.8895	likely_pathogenic	0.9052	pathogenic	-1.52	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	I
I/D	0.9546	likely_pathogenic	0.9611	pathogenic	-2.048	Highly Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	I
I/E	0.8998	likely_pathogenic	0.8958	pathogenic	-1.969	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	I
I/F	0.3543	ambiguous	0.3476	ambiguous	-1.452	Destabilizing	0.323	N	0.439	neutral	None	None	None	None	I
I/G	0.9188	likely_pathogenic	0.9242	pathogenic	-2.596	Highly Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	I
I/H	0.7981	likely_pathogenic	0.8171	pathogenic	-1.816	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
I/K	0.7357	likely_pathogenic	0.741	pathogenic	-1.514	Destabilizing	0.999	D	0.735	prob.delet.	N	0.48085371	None	None	I
I/L	0.2201	likely_benign	0.2282	benign	-1.062	Destabilizing	0.061	N	0.257	neutral	N	0.485919819	None	None	I
I/M	0.222	likely_benign	0.2094	benign	-0.915	Destabilizing	0.994	D	0.561	neutral	N	0.500011603	None	None	I
I/N	0.6904	likely_pathogenic	0.7429	pathogenic	-1.494	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	I
I/P	0.9884	likely_pathogenic	0.9889	pathogenic	-1.409	Destabilizing	0.999	D	0.76	deleterious	None	None	None	None	I
I/Q	0.7794	likely_pathogenic	0.7811	pathogenic	-1.611	Destabilizing	0.999	D	0.764	deleterious	None	None	None	None	I
I/R	0.5868	likely_pathogenic	0.5981	pathogenic	-0.968	Destabilizing	0.999	D	0.763	deleterious	N	0.520954252	None	None	I
I/S	0.6209	likely_pathogenic	0.6763	pathogenic	-2.178	Highly Destabilizing	0.999	D	0.649	neutral	None	None	None	None	I
I/T	0.5992	likely_pathogenic	0.6488	pathogenic	-1.975	Destabilizing	0.99	D	0.578	neutral	N	0.4861641	None	None	I
I/V	0.1264	likely_benign	0.1224	benign	-1.409	Destabilizing	0.817	D	0.458	neutral	N	0.479801062	None	None	I
I/W	0.9003	likely_pathogenic	0.9085	pathogenic	-1.623	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
I/Y	0.7107	likely_pathogenic	0.7361	pathogenic	-1.388	Destabilizing	0.991	D	0.602	neutral	None	None	None	None	I

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.