TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8292	25099;25100;25101	chr2:178718132;178718131;178718130	chr2:179582859;179582858;179582857
N2AB	7975	24148;24149;24150	chr2:178718132;178718131;178718130	chr2:179582859;179582858;179582857
N2A	7048	21367;21368;21369	chr2:178718132;178718131;178718130	chr2:179582859;179582858;179582857
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-68
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.8549
• 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
E/Q	rs778030351	0.355	0.995	N	0.555	0.317	0.342865806769	gnomAD-2.1.1	8.13E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	8.9E-06	0
E/Q	rs778030351	0.355	0.995	N	0.555	0.317	0.342865806769	gnomAD-4.0.0	4.80143E-06	None	None	None	None	I	None	0	2.28676E-05	None	0	0	None	0	0	2.85902E-06	1.43291E-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
E/A	0.3043	likely_benign	0.3084	benign	-0.18	Destabilizing	0.958	D	0.625	neutral	N	0.495984023	None	None	I
E/C	0.9748	likely_pathogenic	0.9757	pathogenic	-0.303	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
E/D	0.1633	likely_benign	0.1753	benign	-0.276	Destabilizing	0.009	N	0.314	neutral	N	0.516127222	None	None	I
E/F	0.9391	likely_pathogenic	0.9443	pathogenic	-0.11	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
E/G	0.4033	ambiguous	0.4212	ambiguous	-0.329	Destabilizing	0.993	D	0.6	neutral	N	0.493774314	None	None	I
E/H	0.7704	likely_pathogenic	0.7921	pathogenic	0.458	Stabilizing	1.0	D	0.584	neutral	None	None	None	None	I
E/I	0.712	likely_pathogenic	0.7096	pathogenic	0.165	Stabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	I
E/K	0.3813	ambiguous	0.4025	ambiguous	0.254	Stabilizing	0.988	D	0.608	neutral	N	0.446901997	None	None	I
E/L	0.7466	likely_pathogenic	0.7405	pathogenic	0.165	Stabilizing	0.995	D	0.694	prob.neutral	None	None	None	None	I
E/M	0.7869	likely_pathogenic	0.7851	pathogenic	-0.055	Destabilizing	0.997	D	0.683	prob.neutral	None	None	None	None	I
E/N	0.4522	ambiguous	0.4941	ambiguous	-0.008	Destabilizing	0.977	D	0.587	neutral	None	None	None	None	I
E/P	0.6605	likely_pathogenic	0.6332	pathogenic	0.068	Stabilizing	0.012	N	0.473	neutral	None	None	None	None	I
E/Q	0.3015	likely_benign	0.314	benign	0.015	Stabilizing	0.995	D	0.555	neutral	N	0.495482591	None	None	I
E/R	0.5707	likely_pathogenic	0.5941	pathogenic	0.572	Stabilizing	0.997	D	0.609	neutral	None	None	None	None	I
E/S	0.3986	ambiguous	0.4082	ambiguous	-0.177	Destabilizing	0.968	D	0.607	neutral	None	None	None	None	I
E/T	0.5264	ambiguous	0.5352	ambiguous	-0.051	Destabilizing	0.997	D	0.57	neutral	None	None	None	None	I
E/V	0.4827	ambiguous	0.4729	ambiguous	0.068	Stabilizing	0.99	D	0.634	neutral	N	0.507990528	None	None	I
E/W	0.9824	likely_pathogenic	0.9829	pathogenic	-0.012	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
E/Y	0.8818	likely_pathogenic	0.8906	pathogenic	0.119	Stabilizing	1.0	D	0.671	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.