TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19497	58714;58715;58716	chr2:178593811;178593810;178593809	chr2:179458538;179458537;179458536
N2AB	17856	53791;53792;53793	chr2:178593811;178593810;178593809	chr2:179458538;179458537;179458536
N2A	16929	51010;51011;51012	chr2:178593811;178593810;178593809	chr2:179458538;179458537;179458536
N2B	10432	31519;31520;31521	chr2:178593811;178593810;178593809	chr2:179458538;179458537;179458536
Novex-1	10557	31894;31895;31896	chr2:178593811;178593810;178593809	chr2:179458538;179458537;179458536
Novex-2	10624	32095;32096;32097	chr2:178593811;178593810;178593809	chr2:179458538;179458537;179458536
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-29
• Domain position: 19
• Structural Position: 20
• Q(SASA): 0.048
• 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
M/I	rs752006805	0.394	0.006	N	0.329	0.163	0.464528537357	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.49E-05	0
M/I	rs752006805	0.394	0.006	N	0.329	0.163	0.464528537357	gnomAD-4.0.0	2.5327E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87876E-05	0	8.2872E-05
M/T	rs375365886	-1.318	0.492	D	0.767	0.397	None	gnomAD-2.1.1	8.09E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	8.96E-06	0
M/T	rs375365886	-1.318	0.492	D	0.767	0.397	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
M/T	rs375365886	-1.318	0.492	D	0.767	0.397	None	gnomAD-4.0.0	1.30194E-05	None	None	None	None	N	None	1.3354E-05	1.669E-05	None	0	0	None	0	0	1.27162E-05	1.0983E-05	4.80677E-05
M/V	rs754532919	-0.13	0.041	N	0.431	0.17	0.43046518545	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	8.96E-06	0
M/V	rs754532919	-0.13	0.041	N	0.431	0.17	0.43046518545	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
M/V	rs754532919	-0.13	0.041	N	0.431	0.17	0.43046518545	gnomAD-4.0.0	6.41185E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.3942E-06	5.36222E-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
M/A	0.6012	likely_pathogenic	0.5402	ambiguous	-1.59	Destabilizing	0.207	N	0.673	neutral	None	None	None	None	N
M/C	0.7763	likely_pathogenic	0.7438	pathogenic	-2.288	Highly Destabilizing	0.981	D	0.788	deleterious	None	None	None	None	N
M/D	0.9984	likely_pathogenic	0.9981	pathogenic	-2.044	Highly Destabilizing	0.932	D	0.819	deleterious	None	None	None	None	N
M/E	0.9868	likely_pathogenic	0.9855	pathogenic	-1.758	Destabilizing	0.818	D	0.81	deleterious	None	None	None	None	N
M/F	0.7348	likely_pathogenic	0.7553	pathogenic	-0.122	Destabilizing	0.002	N	0.367	neutral	None	None	None	None	N
M/G	0.9531	likely_pathogenic	0.9411	pathogenic	-2.09	Highly Destabilizing	0.563	D	0.765	deleterious	None	None	None	None	N
M/H	0.9889	likely_pathogenic	0.988	pathogenic	-2.06	Highly Destabilizing	0.981	D	0.784	deleterious	None	None	None	None	N
M/I	0.4464	ambiguous	0.415	ambiguous	-0.127	Destabilizing	0.006	N	0.329	neutral	N	0.405038653	None	None	N
M/K	0.9598	likely_pathogenic	0.9578	pathogenic	-1.089	Destabilizing	0.492	N	0.787	deleterious	N	0.48315639	None	None	N
M/L	0.2608	likely_benign	0.2561	benign	-0.127	Destabilizing	0.018	N	0.433	neutral	N	0.428622015	None	None	N
M/N	0.9859	likely_pathogenic	0.9837	pathogenic	-1.705	Destabilizing	0.932	D	0.817	deleterious	None	None	None	None	N
M/P	0.9977	likely_pathogenic	0.9977	pathogenic	-0.601	Destabilizing	0.932	D	0.82	deleterious	None	None	None	None	N
M/Q	0.9299	likely_pathogenic	0.9224	pathogenic	-1.223	Destabilizing	0.932	D	0.713	prob.delet.	None	None	None	None	N
M/R	0.9532	likely_pathogenic	0.9518	pathogenic	-1.569	Destabilizing	0.773	D	0.825	deleterious	N	0.48315639	None	None	N
M/S	0.8968	likely_pathogenic	0.8798	pathogenic	-2.061	Highly Destabilizing	0.563	D	0.767	deleterious	None	None	None	None	N
M/T	0.6633	likely_pathogenic	0.6038	pathogenic	-1.64	Destabilizing	0.492	N	0.767	deleterious	D	0.522636615	None	None	N
M/V	0.1046	likely_benign	0.0925	benign	-0.601	Destabilizing	0.041	N	0.431	neutral	N	0.368269776	None	None	N
M/W	0.9843	likely_pathogenic	0.9861	pathogenic	-0.548	Destabilizing	0.944	D	0.776	deleterious	None	None	None	None	N
M/Y	0.9747	likely_pathogenic	0.974	pathogenic	-0.478	Destabilizing	0.241	N	0.799	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.