TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26705	80338;80339;80340	chr2:178566019;178566018;178566017	chr2:179430746;179430745;179430744
N2AB	25064	75415;75416;75417	chr2:178566019;178566018;178566017	chr2:179430746;179430745;179430744
N2A	24137	72634;72635;72636	chr2:178566019;178566018;178566017	chr2:179430746;179430745;179430744
N2B	17640	53143;53144;53145	chr2:178566019;178566018;178566017	chr2:179430746;179430745;179430744
Novex-1	17765	53518;53519;53520	chr2:178566019;178566018;178566017	chr2:179430746;179430745;179430744
Novex-2	17832	53719;53720;53721	chr2:178566019;178566018;178566017	chr2:179430746;179430745;179430744
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-82
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.4502
• 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/D	rs558830502	-0.954	0.002	N	0.315	0.099	0.0666544352282	gnomAD-2.1.1	4.29102E-04	None	None	None	None	N	None	0	0	None	0	6.00123E-03	None	3.27E-05	None	0	7.83E-06	1.40766E-04
E/D	rs558830502	-0.954	0.002	N	0.315	0.099	0.0666544352282	gnomAD-3.1.2	1.77529E-04	None	None	None	None	N	None	0	0	0	0	4.83559E-03	None	0	0	1.47E-05	2.06954E-04	0
E/D	rs558830502	-0.954	0.002	N	0.315	0.099	0.0666544352282	1000 genomes	5.99042E-04	None	None	None	None	N	None	0	0	None	None	3E-03	0	None	None	None	0	None
E/D	rs558830502	-0.954	0.002	N	0.315	0.099	0.0666544352282	gnomAD-4.0.0	1.3263E-04	None	None	None	None	N	None	0	0	None	0	4.21517E-03	None	0	0	2.54322E-06	3.29439E-05	3.04185E-04
E/K	rs758610676	-0.435	0.002	N	0.379	0.232	0.18995819373	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
E/K	rs758610676	-0.435	0.002	N	0.379	0.232	0.18995819373	gnomAD-4.0.0	2.7373E-06	None	None	None	None	N	None	0	2.23674E-05	None	0	2.51991E-05	None	0	0	1.7992E-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	0.2566	likely_benign	0.3111	benign	-0.793	Destabilizing	0.201	N	0.625	neutral	N	0.521599252	None	None	N
E/C	0.8668	likely_pathogenic	0.9055	pathogenic	-0.374	Destabilizing	0.982	D	0.732	prob.delet.	None	None	None	None	N
E/D	0.0819	likely_benign	0.102	benign	-0.919	Destabilizing	0.002	N	0.315	neutral	N	0.437769934	None	None	N
E/F	0.8339	likely_pathogenic	0.8765	pathogenic	-0.55	Destabilizing	0.982	D	0.76	deleterious	None	None	None	None	N
E/G	0.2757	likely_benign	0.3586	ambiguous	-1.097	Destabilizing	0.334	N	0.682	prob.neutral	N	0.48190585	None	None	N
E/H	0.6321	likely_pathogenic	0.6952	pathogenic	-0.796	Destabilizing	0.947	D	0.617	neutral	None	None	None	None	N
E/I	0.5415	ambiguous	0.5661	pathogenic	0.017	Stabilizing	0.826	D	0.775	deleterious	None	None	None	None	N
E/K	0.376	ambiguous	0.4246	ambiguous	-0.623	Destabilizing	0.002	N	0.379	neutral	N	0.461241439	None	None	N
E/L	0.5054	ambiguous	0.5545	ambiguous	0.017	Stabilizing	0.7	D	0.745	deleterious	None	None	None	None	N
E/M	0.5577	ambiguous	0.5951	pathogenic	0.416	Stabilizing	0.982	D	0.759	deleterious	None	None	None	None	N
E/N	0.2206	likely_benign	0.2795	benign	-0.871	Destabilizing	0.539	D	0.612	neutral	None	None	None	None	N
E/P	0.9703	likely_pathogenic	0.9813	pathogenic	-0.232	Destabilizing	0.826	D	0.759	deleterious	None	None	None	None	N
E/Q	0.2172	likely_benign	0.2378	benign	-0.786	Destabilizing	0.638	D	0.568	neutral	N	0.505379006	None	None	N
E/R	0.5748	likely_pathogenic	0.6335	pathogenic	-0.379	Destabilizing	0.539	D	0.611	neutral	None	None	None	None	N
E/S	0.2319	likely_benign	0.2849	benign	-1.15	Destabilizing	0.25	N	0.519	neutral	None	None	None	None	N
E/T	0.324	likely_benign	0.3593	ambiguous	-0.916	Destabilizing	0.7	D	0.726	prob.delet.	None	None	None	None	N
E/V	0.3649	ambiguous	0.3801	ambiguous	-0.232	Destabilizing	0.638	D	0.744	deleterious	N	0.481652361	None	None	N
E/W	0.9437	likely_pathogenic	0.9637	pathogenic	-0.398	Destabilizing	0.982	D	0.723	prob.delet.	None	None	None	None	N
E/Y	0.6782	likely_pathogenic	0.7635	pathogenic	-0.347	Destabilizing	0.935	D	0.776	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.