TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16113	48562;48563;48564	chr2:178615764;178615763;178615762	chr2:179480491;179480490;179480489
N2AB	14472	43639;43640;43641	chr2:178615764;178615763;178615762	chr2:179480491;179480490;179480489
N2A	13545	40858;40859;40860	chr2:178615764;178615763;178615762	chr2:179480491;179480490;179480489
N2B	7048	21367;21368;21369	chr2:178615764;178615763;178615762	chr2:179480491;179480490;179480489
Novex-1	7173	21742;21743;21744	chr2:178615764;178615763;178615762	chr2:179480491;179480490;179480489
Novex-2	7240	21943;21944;21945	chr2:178615764;178615763;178615762	chr2:179480491;179480490;179480489
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: Fn3-4
• Domain position: 59
• Structural Position: 90
• Q(SASA): 0.457
• 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/D	None	None	0.999	N	0.471	0.27	0.187945064343	gnomAD-4.0.0	1.59558E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43542E-05	0
E/K	rs548275593	-0.524	0.999	N	0.591	0.402	0.352693368174	gnomAD-2.1.1	6.86E-05	None	None	None	None	I	None	0	0	None	0	0	None	5.57304E-04	None	0	0	0
E/K	rs548275593	-0.524	0.999	N	0.591	0.402	0.352693368174	gnomAD-3.1.2	2.63E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	8.285E-04	0
E/K	rs548275593	-0.524	0.999	N	0.591	0.402	0.352693368174	gnomAD-4.0.0	3.72259E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.48808E-04	1.60333E-05

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	0.1809	likely_benign	0.221	benign	-0.724	Destabilizing	0.999	D	0.699	prob.neutral	N	0.47836658	None	None	I
E/C	0.7842	likely_pathogenic	0.8516	pathogenic	-0.476	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
E/D	0.2528	likely_benign	0.3248	benign	-1.13	Destabilizing	0.999	D	0.471	neutral	N	0.511967271	None	None	I
E/F	0.8246	likely_pathogenic	0.8811	pathogenic	0.119	Stabilizing	1.0	D	0.832	deleterious	None	None	None	None	I
E/G	0.2553	likely_benign	0.3212	benign	-1.136	Destabilizing	1.0	D	0.743	deleterious	N	0.500807618	None	None	I
E/H	0.4515	ambiguous	0.5926	pathogenic	-0.122	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
E/I	0.5344	ambiguous	0.6119	pathogenic	0.417	Stabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
E/K	0.2467	likely_benign	0.3469	ambiguous	-0.722	Destabilizing	0.999	D	0.591	neutral	N	0.482459585	None	None	I
E/L	0.5943	likely_pathogenic	0.7062	pathogenic	0.417	Stabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
E/M	0.5572	ambiguous	0.6449	pathogenic	0.818	Stabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
E/N	0.3445	ambiguous	0.4435	ambiguous	-1.283	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
E/P	0.9506	likely_pathogenic	0.9716	pathogenic	0.059	Stabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
E/Q	0.1306	likely_benign	0.1803	benign	-1.079	Destabilizing	1.0	D	0.661	neutral	N	0.480503793	None	None	I
E/R	0.3271	likely_benign	0.4394	ambiguous	-0.35	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	I
E/S	0.1898	likely_benign	0.2364	benign	-1.635	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	I
E/T	0.2207	likely_benign	0.2782	benign	-1.286	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	I
E/V	0.3053	likely_benign	0.3635	ambiguous	0.059	Stabilizing	1.0	D	0.789	deleterious	N	0.501612672	None	None	I
E/W	0.9307	likely_pathogenic	0.9598	pathogenic	0.388	Stabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
E/Y	0.6956	likely_pathogenic	0.782	pathogenic	0.372	Stabilizing	1.0	D	0.825	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.