TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8570	25933;25934;25935	chr2:178715706;178715705;178715704	chr2:179580433;179580432;179580431
N2AB	8253	24982;24983;24984	chr2:178715706;178715705;178715704	chr2:179580433;179580432;179580431
N2A	7326	22201;22202;22203	chr2:178715706;178715705;178715704	chr2:179580433;179580432;179580431
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-71
• Domain position: 22
• Structural Position: 31
• Q(SASA): 0.4381
• 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/K	rs552462622	-0.253	0.883	N	0.487	0.404	None	gnomAD-2.1.1	4.12E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.08E-05	8.26E-05	0
E/K	rs552462622	-0.253	0.883	N	0.487	0.404	None	gnomAD-3.1.2	7.23E-05	None	None	None	None	N	None	9.66E-05	0	0	0	0	None	0	0	1.02938E-04	0	0
E/K	rs552462622	-0.253	0.883	N	0.487	0.404	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
E/K	rs552462622	-0.253	0.883	N	0.487	0.404	None	gnomAD-4.0.0	1.44985E-04	None	None	None	None	N	None	5.33732E-05	0	None	0	0	None	4.71313E-05	0	1.9045E-04	0	3.21399E-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	0.2397	likely_benign	0.2249	benign	-0.755	Destabilizing	0.804	D	0.553	neutral	N	0.489708936	None	None	N
E/C	0.9333	likely_pathogenic	0.9328	pathogenic	-0.526	Destabilizing	0.998	D	0.714	prob.delet.	None	None	None	None	N
E/D	0.232	likely_benign	0.2453	benign	-1.133	Destabilizing	0.001	N	0.224	neutral	D	0.526498931	None	None	N
E/F	0.8315	likely_pathogenic	0.8366	pathogenic	-0.199	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
E/G	0.3887	ambiguous	0.3749	ambiguous	-1.111	Destabilizing	0.932	D	0.609	neutral	D	0.530730065	None	None	N
E/H	0.5714	likely_pathogenic	0.5845	pathogenic	-0.447	Destabilizing	0.998	D	0.665	neutral	None	None	None	None	N
E/I	0.4063	ambiguous	0.3875	ambiguous	0.212	Stabilizing	0.971	D	0.747	deleterious	None	None	None	None	N
E/K	0.2803	likely_benign	0.274	benign	-0.694	Destabilizing	0.883	D	0.487	neutral	N	0.496265848	None	None	N
E/L	0.5448	ambiguous	0.5366	ambiguous	0.212	Stabilizing	0.971	D	0.723	prob.delet.	None	None	None	None	N
E/M	0.5859	likely_pathogenic	0.5692	pathogenic	0.535	Stabilizing	0.986	D	0.713	prob.delet.	None	None	None	None	N
E/N	0.4286	ambiguous	0.4339	ambiguous	-1.14	Destabilizing	0.793	D	0.622	neutral	None	None	None	None	N
E/P	0.9498	likely_pathogenic	0.9499	pathogenic	-0.089	Destabilizing	0.833	D	0.739	prob.delet.	None	None	None	None	N
E/Q	0.1664	likely_benign	0.1642	benign	-1.004	Destabilizing	0.975	D	0.611	neutral	N	0.485251937	None	None	N
E/R	0.4165	ambiguous	0.4234	ambiguous	-0.373	Destabilizing	0.986	D	0.66	neutral	None	None	None	None	N
E/S	0.2725	likely_benign	0.2644	benign	-1.419	Destabilizing	0.844	D	0.497	neutral	None	None	None	None	N
E/T	0.277	likely_benign	0.2679	benign	-1.131	Destabilizing	0.963	D	0.688	prob.neutral	None	None	None	None	N
E/V	0.2535	likely_benign	0.2399	benign	-0.089	Destabilizing	0.947	D	0.702	prob.neutral	N	0.504485509	None	None	N
E/W	0.9544	likely_pathogenic	0.9579	pathogenic	0.02	Stabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
E/Y	0.7653	likely_pathogenic	0.7724	pathogenic	0.03	Stabilizing	1.0	D	0.731	prob.delet.	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.