TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18634	56125;56126;56127	chr2:178601004;178601003;178601002	chr2:179465731;179465730;179465729
N2AB	16993	51202;51203;51204	chr2:178601004;178601003;178601002	chr2:179465731;179465730;179465729
N2A	16066	48421;48422;48423	chr2:178601004;178601003;178601002	chr2:179465731;179465730;179465729
N2B	9569	28930;28931;28932	chr2:178601004;178601003;178601002	chr2:179465731;179465730;179465729
Novex-1	9694	29305;29306;29307	chr2:178601004;178601003;178601002	chr2:179465731;179465730;179465729
Novex-2	9761	29506;29507;29508	chr2:178601004;178601003;178601002	chr2:179465731;179465730;179465729
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Fn3-23
• Domain position: 56
• Structural Position: 68
• Q(SASA): 0.2432
• 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
C/R	rs2154192588	None	0.999	N	0.764	0.519	0.818176495643	gnomAD-4.0.0	3.18529E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.72213E-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
C/A	0.7153	likely_pathogenic	0.6724	pathogenic	-1.999	Destabilizing	0.964	D	0.468	neutral	None	None	None	None	I
C/D	0.9862	likely_pathogenic	0.9814	pathogenic	-0.661	Destabilizing	0.999	D	0.756	deleterious	None	None	None	None	I
C/E	0.9858	likely_pathogenic	0.9804	pathogenic	-0.52	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	I
C/F	0.6549	likely_pathogenic	0.6093	pathogenic	-1.289	Destabilizing	0.997	D	0.724	prob.delet.	N	0.508203093	None	None	I
C/G	0.6748	likely_pathogenic	0.5924	pathogenic	-2.337	Highly Destabilizing	0.999	D	0.699	prob.neutral	N	0.482761089	None	None	I
C/H	0.915	likely_pathogenic	0.8901	pathogenic	-2.292	Highly Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
C/I	0.7549	likely_pathogenic	0.73	pathogenic	-1.108	Destabilizing	0.971	D	0.498	neutral	None	None	None	None	I
C/K	0.9753	likely_pathogenic	0.9638	pathogenic	-1.214	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	I
C/L	0.768	likely_pathogenic	0.742	pathogenic	-1.108	Destabilizing	0.931	D	0.516	neutral	None	None	None	None	I
C/M	0.8654	likely_pathogenic	0.8434	pathogenic	0.039	Stabilizing	0.998	D	0.707	prob.neutral	None	None	None	None	I
C/N	0.933	likely_pathogenic	0.914	pathogenic	-1.354	Destabilizing	0.999	D	0.764	deleterious	None	None	None	None	I
C/P	0.9903	likely_pathogenic	0.9873	pathogenic	-1.38	Destabilizing	0.999	D	0.764	deleterious	None	None	None	None	I
C/Q	0.9464	likely_pathogenic	0.9223	pathogenic	-1.155	Destabilizing	0.999	D	0.759	deleterious	None	None	None	None	I
C/R	0.8797	likely_pathogenic	0.8244	pathogenic	-1.153	Destabilizing	0.999	D	0.764	deleterious	N	0.507484708	None	None	I
C/S	0.7921	likely_pathogenic	0.7451	pathogenic	-1.894	Destabilizing	0.99	D	0.595	neutral	N	0.470226241	None	None	I
C/T	0.8443	likely_pathogenic	0.8258	pathogenic	-1.559	Destabilizing	0.985	D	0.555	neutral	None	None	None	None	I
C/V	0.6216	likely_pathogenic	0.608	pathogenic	-1.38	Destabilizing	0.469	N	0.342	neutral	None	None	None	None	I
C/W	0.8938	likely_pathogenic	0.8626	pathogenic	-1.318	Destabilizing	1.0	D	0.719	prob.delet.	N	0.510273093	None	None	I
C/Y	0.7545	likely_pathogenic	0.7109	pathogenic	-1.318	Destabilizing	0.999	D	0.731	prob.delet.	N	0.474518655	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.