TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19222	57889;57890;57891	chr2:178595690;178595689;178595688	chr2:179460417;179460416;179460415
N2AB	17581	52966;52967;52968	chr2:178595690;178595689;178595688	chr2:179460417;179460416;179460415
N2A	16654	50185;50186;50187	chr2:178595690;178595689;178595688	chr2:179460417;179460416;179460415
N2B	10157	30694;30695;30696	chr2:178595690;178595689;178595688	chr2:179460417;179460416;179460415
Novex-1	10282	31069;31070;31071	chr2:178595690;178595689;178595688	chr2:179460417;179460416;179460415
Novex-2	10349	31270;31271;31272	chr2:178595690;178595689;178595688	chr2:179460417;179460416;179460415
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: 40
• Structural Position: 41
• Q(SASA): 0.1507
• 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
E/A	None	None	0.41	N	0.68	0.457	0.392855499163	gnomAD-4.0.0	6.86457E-07	None	None	None	None	N	None	2.99133E-05	0	None	0	0	None	0	0	0	0	0
E/G	rs572862573	-2.764	0.83	N	0.781	0.475	0.48763082235	gnomAD-2.1.1	7.07E-05	None	None	None	None	N	None	0	0	None	0	0	None	5.16636E-04	None	0	0	3.39443E-04
E/G	rs572862573	-2.764	0.83	N	0.781	0.475	0.48763082235	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07383E-04	0
E/G	rs572862573	-2.764	0.83	N	0.781	0.475	0.48763082235	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
E/G	rs572862573	-2.764	0.83	N	0.781	0.475	0.48763082235	gnomAD-4.0.0	2.85905E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	1.65125E-04	8.49117E-07	4.67873E-04	3.20821E-05
E/K	rs2051376296	None	0.41	N	0.673	0.256	0.263612267334	gnomAD-4.0.0	6.86556E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.01237E-07	0	0
E/V	rs572862573	-1.177	0.83	N	0.808	0.497	0.619387179241	gnomAD-2.1.1	4.16E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.19E-06	0
E/V	rs572862573	-1.177	0.83	N	0.808	0.497	0.619387179241	gnomAD-4.0.0	6.86457E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.66041E-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	0.8809	likely_pathogenic	0.8918	pathogenic	-0.864	Destabilizing	0.41	N	0.68	prob.neutral	N	0.520543443	None	None	N
E/C	0.9836	likely_pathogenic	0.9854	pathogenic	-0.111	Destabilizing	0.993	D	0.793	deleterious	None	None	None	None	N
E/D	0.8507	likely_pathogenic	0.842	pathogenic	-1.669	Destabilizing	0.581	D	0.623	neutral	N	0.483600917	None	None	N
E/F	0.9917	likely_pathogenic	0.9932	pathogenic	-0.615	Destabilizing	0.993	D	0.837	deleterious	None	None	None	None	N
E/G	0.9192	likely_pathogenic	0.936	pathogenic	-1.258	Destabilizing	0.83	D	0.781	deleterious	N	0.51079698	None	None	N
E/H	0.9719	likely_pathogenic	0.972	pathogenic	-0.501	Destabilizing	0.961	D	0.83	deleterious	None	None	None	None	N
E/I	0.973	likely_pathogenic	0.9806	pathogenic	0.261	Stabilizing	0.929	D	0.841	deleterious	None	None	None	None	N
E/K	0.925	likely_pathogenic	0.9313	pathogenic	-0.802	Destabilizing	0.41	N	0.673	neutral	N	0.4963988	None	None	N
E/L	0.9674	likely_pathogenic	0.9633	pathogenic	0.261	Stabilizing	0.866	D	0.818	deleterious	None	None	None	None	N
E/M	0.9471	likely_pathogenic	0.9583	pathogenic	0.846	Stabilizing	0.98	D	0.831	deleterious	None	None	None	None	N
E/N	0.97	likely_pathogenic	0.9688	pathogenic	-1.165	Destabilizing	0.866	D	0.814	deleterious	None	None	None	None	N
E/P	0.9998	likely_pathogenic	0.9998	pathogenic	-0.099	Destabilizing	0.929	D	0.819	deleterious	None	None	None	None	N
E/Q	0.4618	ambiguous	0.492	ambiguous	-0.814	Destabilizing	0.01	N	0.375	neutral	N	0.510072749	None	None	N
E/R	0.9441	likely_pathogenic	0.9488	pathogenic	-0.837	Destabilizing	0.764	D	0.815	deleterious	None	None	None	None	N
E/S	0.8872	likely_pathogenic	0.9047	pathogenic	-1.681	Destabilizing	0.48	N	0.709	prob.delet.	None	None	None	None	N
E/T	0.9537	likely_pathogenic	0.9655	pathogenic	-1.292	Destabilizing	0.866	D	0.787	deleterious	None	None	None	None	N
E/V	0.9334	likely_pathogenic	0.9504	pathogenic	-0.099	Destabilizing	0.83	D	0.808	deleterious	N	0.514555961	None	None	N
E/W	0.9958	likely_pathogenic	0.9969	pathogenic	-0.829	Destabilizing	0.993	D	0.801	deleterious	None	None	None	None	N
E/Y	0.9882	likely_pathogenic	0.9896	pathogenic	-0.431	Destabilizing	0.929	D	0.837	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.