TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16905	50938;50939;50940	chr2:178611516;178611515;178611514	chr2:179476243;179476242;179476241
N2AB	15264	46015;46016;46017	chr2:178611516;178611515;178611514	chr2:179476243;179476242;179476241
N2A	14337	43234;43235;43236	chr2:178611516;178611515;178611514	chr2:179476243;179476242;179476241
N2B	7840	23743;23744;23745	chr2:178611516;178611515;178611514	chr2:179476243;179476242;179476241
Novex-1	7965	24118;24119;24120	chr2:178611516;178611515;178611514	chr2:179476243;179476242;179476241
Novex-2	8032	24319;24320;24321	chr2:178611516;178611515;178611514	chr2:179476243;179476242;179476241
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Fn3-11
• Domain position: 54
• Structural Position: 72
• Q(SASA): 0.6356
• 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
R/C	rs267599049	-0.287	1.0	D	0.776	0.412	0.642361509819	gnomAD-2.1.1	5.66E-05	None	None	None	None	I	None	6.47E-05	0	None	0	5.6E-05	None	2.61523E-04	None	0	3.59E-05	0
R/C	rs267599049	-0.287	1.0	D	0.776	0.412	0.642361509819	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
R/C	rs267599049	-0.287	1.0	D	0.776	0.412	0.642361509819	gnomAD-4.0.0	1.86013E-05	None	None	None	None	I	None	1.33697E-05	0	None	0	1.11792E-04	None	0	0	5.9358E-06	1.64719E-04	3.20441E-05
R/H	rs191539637	-0.617	1.0	N	0.754	0.386	None	gnomAD-2.1.1	4.70117E-04	None	None	None	None	I	None	2.06902E-04	5.66E-05	None	2.42483E-03	3.09725E-04	None	3.27E-05	None	9.19559E-04	4.96885E-04	8.45309E-04
R/H	rs191539637	-0.617	1.0	N	0.754	0.386	None	gnomAD-3.1.2	5.26794E-04	None	None	None	None	I	None	9.66E-05	6.56E-05	0	2.88184E-03	3.9032E-04	None	1.69907E-03	0	6.62681E-04	0	0
R/H	rs191539637	-0.617	1.0	N	0.754	0.386	None	1000 genomes	3.99361E-04	None	None	None	None	I	None	0	1.4E-03	None	None	1E-03	0	None	None	None	0	None
R/H	rs191539637	-0.617	1.0	N	0.754	0.386	None	gnomAD-4.0.0	3.66426E-04	None	None	None	None	I	None	1.20122E-04	6.672E-05	None	3.07578E-03	1.34192E-04	None	1.21913E-03	0	3.26476E-04	1.09818E-05	2.72296E-04
R/P	rs191539637	-0.225	1.0	N	0.691	0.387	0.364730456448	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
R/P	rs191539637	-0.225	1.0	N	0.691	0.387	0.364730456448	gnomAD-4.0.0	1.36902E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15958E-05	1.65782E-05
R/S	rs267599049	0.111	1.0	N	0.672	0.421	0.31501682445	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	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
R/A	0.7337	likely_pathogenic	0.7886	pathogenic	0.044	Stabilizing	0.999	D	0.611	neutral	None	None	None	None	I
R/C	0.3671	ambiguous	0.4072	ambiguous	-0.14	Destabilizing	1.0	D	0.776	deleterious	D	0.550888858	None	None	I
R/D	0.8962	likely_pathogenic	0.9195	pathogenic	-0.26	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
R/E	0.7166	likely_pathogenic	0.7464	pathogenic	-0.217	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	I
R/F	0.804	likely_pathogenic	0.836	pathogenic	-0.257	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
R/G	0.6123	likely_pathogenic	0.6733	pathogenic	-0.107	Destabilizing	1.0	D	0.616	neutral	N	0.440274827	None	None	I
R/H	0.2049	likely_benign	0.2204	benign	-0.635	Destabilizing	1.0	D	0.754	deleterious	N	0.48132334	None	None	I
R/I	0.5466	ambiguous	0.6151	pathogenic	0.397	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
R/K	0.1908	likely_benign	0.1872	benign	-0.094	Destabilizing	0.998	D	0.53	neutral	None	None	None	None	I
R/L	0.487	ambiguous	0.5524	ambiguous	0.397	Stabilizing	1.0	D	0.616	neutral	N	0.475267477	None	None	I
R/M	0.6028	likely_pathogenic	0.6665	pathogenic	-0.008	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
R/N	0.8329	likely_pathogenic	0.8648	pathogenic	0.062	Stabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	I
R/P	0.9343	likely_pathogenic	0.9365	pathogenic	0.298	Stabilizing	1.0	D	0.691	prob.neutral	N	0.470339484	None	None	I
R/Q	0.2032	likely_benign	0.2217	benign	-0.004	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	I
R/S	0.7866	likely_pathogenic	0.8289	pathogenic	-0.148	Destabilizing	1.0	D	0.672	neutral	N	0.460085859	None	None	I
R/T	0.5906	likely_pathogenic	0.6557	pathogenic	0.005	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	I
R/V	0.6281	likely_pathogenic	0.6807	pathogenic	0.298	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
R/W	0.4137	ambiguous	0.4724	ambiguous	-0.415	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
R/Y	0.6665	likely_pathogenic	0.7138	pathogenic	-0.006	Destabilizing	1.0	D	0.726	prob.delet.	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.