TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19261	58006;58007;58008	chr2:178595573;178595572;178595571	chr2:179460300;179460299;179460298
N2AB	17620	53083;53084;53085	chr2:178595573;178595572;178595571	chr2:179460300;179460299;179460298
N2A	16693	50302;50303;50304	chr2:178595573;178595572;178595571	chr2:179460300;179460299;179460298
N2B	10196	30811;30812;30813	chr2:178595573;178595572;178595571	chr2:179460300;179460299;179460298
Novex-1	10321	31186;31187;31188	chr2:178595573;178595572;178595571	chr2:179460300;179460299;179460298
Novex-2	10388	31387;31388;31389	chr2:178595573;178595572;178595571	chr2:179460300;179460299;179460298
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: Fn3-27
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.1748
• 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/A	rs1454108057	None	0.999	N	0.612	0.472	0.358744678677	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/D	None	None	0.999	N	0.465	0.293	0.331365685468	gnomAD-4.0.0	1.40367E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.83211E-06	0	0
E/K	rs200311184	-0.531	0.999	N	0.475	0.395	None	gnomAD-2.1.1	5.11E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.21E-05	0
E/K	rs200311184	-0.531	0.999	N	0.475	0.395	None	gnomAD-4.0.0	1.68943E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.03174E-06	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
E/A	0.6207	likely_pathogenic	0.6833	pathogenic	-0.484	Destabilizing	0.999	D	0.612	neutral	N	0.510032677	None	None	I
E/C	0.9388	likely_pathogenic	0.9529	pathogenic	-0.531	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
E/D	0.9326	likely_pathogenic	0.944	pathogenic	-1.347	Destabilizing	0.999	D	0.465	neutral	N	0.495891821	None	None	I
E/F	0.9835	likely_pathogenic	0.9887	pathogenic	-1.037	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
E/G	0.8087	likely_pathogenic	0.8359	pathogenic	-0.777	Destabilizing	1.0	D	0.733	prob.delet.	N	0.491118881	None	None	I
E/H	0.9449	likely_pathogenic	0.9586	pathogenic	-1.226	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	I
E/I	0.7473	likely_pathogenic	0.8216	pathogenic	0.287	Stabilizing	1.0	D	0.871	deleterious	None	None	None	None	I
E/K	0.6449	likely_pathogenic	0.7236	pathogenic	-0.699	Destabilizing	0.999	D	0.475	neutral	N	0.465417302	None	None	I
E/L	0.9283	likely_pathogenic	0.9477	pathogenic	0.287	Stabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
E/M	0.8422	likely_pathogenic	0.8881	pathogenic	0.678	Stabilizing	1.0	D	0.846	deleterious	None	None	None	None	I
E/N	0.9425	likely_pathogenic	0.9561	pathogenic	-0.888	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	I
E/P	0.9987	likely_pathogenic	0.9987	pathogenic	0.052	Stabilizing	1.0	D	0.766	deleterious	None	None	None	None	I
E/Q	0.3322	likely_benign	0.3882	ambiguous	-0.744	Destabilizing	1.0	D	0.596	neutral	N	0.469923526	None	None	I
E/R	0.7606	likely_pathogenic	0.8103	pathogenic	-0.795	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	I
E/S	0.7626	likely_pathogenic	0.8162	pathogenic	-1.302	Destabilizing	0.999	D	0.53	neutral	None	None	None	None	I
E/T	0.7727	likely_pathogenic	0.8262	pathogenic	-1.034	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
E/V	0.4677	ambiguous	0.5631	ambiguous	0.052	Stabilizing	1.0	D	0.785	deleterious	N	0.441839241	None	None	I
E/W	0.9953	likely_pathogenic	0.9965	pathogenic	-1.348	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	I
E/Y	0.9782	likely_pathogenic	0.9854	pathogenic	-0.897	Destabilizing	1.0	D	0.839	deleterious	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.