TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33139	99640;99641;99642	chr2:178537792;178537791;178537790	chr2:179402519;179402518;179402517
N2AB	31498	94717;94718;94719	chr2:178537792;178537791;178537790	chr2:179402519;179402518;179402517
N2A	30571	91936;91937;91938	chr2:178537792;178537791;178537790	chr2:179402519;179402518;179402517
N2B	24074	72445;72446;72447	chr2:178537792;178537791;178537790	chr2:179402519;179402518;179402517
Novex-1	24199	72820;72821;72822	chr2:178537792;178537791;178537790	chr2:179402519;179402518;179402517
Novex-2	24266	73021;73022;73023	chr2:178537792;178537791;178537790	chr2:179402519;179402518;179402517
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-156
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.6381
• 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
K/E	rs779723670	0.359	0.974	N	0.562	0.38	0.366277470483	gnomAD-2.1.1	1.61E-05	None	None	None	None	I	None	6.46E-05	5.8E-05	None	0	0	None	0	None	0	8.86E-06	0
K/E	rs779723670	0.359	0.974	N	0.562	0.38	0.366277470483	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	2.94E-05	0	0
K/E	rs779723670	0.359	0.974	N	0.562	0.38	0.366277470483	gnomAD-4.0.0	2.41682E-05	None	None	None	None	I	None	2.66973E-05	3.33456E-05	None	0	0	None	0	0	2.79711E-05	0	3.20225E-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
K/A	0.7837	likely_pathogenic	0.7806	pathogenic	-0.162	Destabilizing	0.997	D	0.598	neutral	None	None	None	None	I
K/C	0.8932	likely_pathogenic	0.9098	pathogenic	-0.482	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	I
K/D	0.8527	likely_pathogenic	0.8438	pathogenic	0.185	Stabilizing	0.999	D	0.657	neutral	None	None	None	None	I
K/E	0.3756	ambiguous	0.3462	ambiguous	0.254	Stabilizing	0.974	D	0.562	neutral	N	0.472509731	None	None	I
K/F	0.9528	likely_pathogenic	0.9573	pathogenic	-0.122	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	I
K/G	0.8385	likely_pathogenic	0.8427	pathogenic	-0.427	Destabilizing	0.999	D	0.555	neutral	None	None	None	None	I
K/H	0.5348	ambiguous	0.56	ambiguous	-0.534	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	I
K/I	0.7018	likely_pathogenic	0.7004	pathogenic	0.481	Stabilizing	0.988	D	0.701	prob.neutral	D	0.523960058	None	None	I
K/L	0.751	likely_pathogenic	0.7384	pathogenic	0.481	Stabilizing	0.972	D	0.555	neutral	None	None	None	None	I
K/M	0.5644	likely_pathogenic	0.5479	ambiguous	0.028	Stabilizing	0.999	D	0.657	neutral	None	None	None	None	I
K/N	0.6947	likely_pathogenic	0.6897	pathogenic	-0.136	Destabilizing	0.999	D	0.628	neutral	D	0.525056136	None	None	I
K/P	0.9901	likely_pathogenic	0.9906	pathogenic	0.296	Stabilizing	1.0	D	0.639	neutral	None	None	None	None	I
K/Q	0.2334	likely_benign	0.2443	benign	-0.173	Destabilizing	0.981	D	0.617	neutral	N	0.499272258	None	None	I
K/R	0.0959	likely_benign	0.1015	benign	-0.152	Destabilizing	0.143	N	0.307	neutral	N	0.510702759	None	None	I
K/S	0.7732	likely_pathogenic	0.7796	pathogenic	-0.668	Destabilizing	0.997	D	0.576	neutral	None	None	None	None	I
K/T	0.502	ambiguous	0.4845	ambiguous	-0.421	Destabilizing	0.996	D	0.611	neutral	N	0.495253304	None	None	I
K/V	0.6546	likely_pathogenic	0.6535	pathogenic	0.296	Stabilizing	0.978	D	0.661	neutral	None	None	None	None	I
K/W	0.9375	likely_pathogenic	0.9454	pathogenic	-0.126	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
K/Y	0.8825	likely_pathogenic	0.8878	pathogenic	0.201	Stabilizing	0.994	D	0.669	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.