TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27176	81751;81752;81753	chr2:178564606;178564605;178564604	chr2:179429333;179429332;179429331
N2AB	25535	76828;76829;76830	chr2:178564606;178564605;178564604	chr2:179429333;179429332;179429331
N2A	24608	74047;74048;74049	chr2:178564606;178564605;178564604	chr2:179429333;179429332;179429331
N2B	18111	54556;54557;54558	chr2:178564606;178564605;178564604	chr2:179429333;179429332;179429331
Novex-1	18236	54931;54932;54933	chr2:178564606;178564605;178564604	chr2:179429333;179429332;179429331
Novex-2	18303	55132;55133;55134	chr2:178564606;178564605;178564604	chr2:179429333;179429332;179429331
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Fn3-86
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.7781
• 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
R/C	rs778385749	-0.188	0.999	N	0.407	0.334	0.567569374525	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	1.78E-05	0
R/C	rs778385749	-0.188	0.999	N	0.407	0.334	0.567569374525	gnomAD-4.0.0	2.66894E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.23833E-05	1.15969E-05	3.31422E-05
R/G	rs778385749	None	0.911	N	0.496	0.232	0.421184727016	gnomAD-4.0.0	2.73738E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59814E-06	0	0
R/H	rs199726308	-0.674	0.994	N	0.523	0.24	0.295974979623	gnomAD-2.1.1	3.58E-05	None	None	None	None	N	None	0	0	None	0	4.643E-04	None	0	None	0	0	1.40885E-04
R/H	rs199726308	-0.674	0.994	N	0.523	0.24	0.295974979623	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	1.92976E-04	None	0	0	2.94E-05	0	0
R/H	rs199726308	-0.674	0.994	N	0.523	0.24	0.295974979623	gnomAD-4.0.0	7.43805E-06	None	None	None	None	N	None	0	0	None	0	6.70271E-05	None	0	0	5.08607E-06	3.29431E-05	0
R/L	rs199726308	0.335	0.911	N	0.475	0.209	None	gnomAD-2.1.1	1.18033E-04	None	None	None	None	N	None	0	8.5E-05	None	0	0	None	0	None	0	2.34859E-04	0
R/L	rs199726308	0.335	0.911	N	0.475	0.209	None	gnomAD-3.1.2	1.7754E-04	None	None	None	None	N	None	2.41E-05	2.62158E-04	0	0	0	None	0	0	3.23482E-04	0	0
R/L	rs199726308	0.335	0.911	N	0.475	0.209	None	gnomAD-4.0.0	1.62397E-04	None	None	None	None	N	None	1.33561E-05	1.3344E-04	None	0	0	None	6.25313E-05	0	2.11072E-04	0	0
R/S	None	-0.105	0.679	N	0.47	0.203	0.264081493735	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.61E-05	None	0	None	0	0	0
R/S	None	-0.105	0.679	N	0.47	0.203	0.264081493735	gnomAD-4.0.0	6.84347E-07	None	None	None	None	N	None	0	0	None	0	2.5264E-05	None	0	0	0	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
R/A	0.2739	likely_benign	0.2576	benign	-0.632	Destabilizing	0.688	D	0.478	neutral	None	None	None	None	N
R/C	0.1183	likely_benign	0.1195	benign	-0.576	Destabilizing	0.999	D	0.407	neutral	N	0.467280635	None	None	N
R/D	0.6278	likely_pathogenic	0.6032	pathogenic	-0.152	Destabilizing	0.842	D	0.5	neutral	None	None	None	None	N
R/E	0.2925	likely_benign	0.2658	benign	-0.097	Destabilizing	0.525	D	0.454	neutral	None	None	None	None	N
R/F	0.4038	ambiguous	0.3809	ambiguous	-0.898	Destabilizing	0.991	D	0.427	neutral	None	None	None	None	N
R/G	0.269	likely_benign	0.2385	benign	-0.835	Destabilizing	0.911	D	0.496	neutral	N	0.458969138	None	None	N
R/H	0.1009	likely_benign	0.1008	benign	-1.196	Destabilizing	0.994	D	0.523	neutral	N	0.466520166	None	None	N
R/I	0.1691	likely_benign	0.1513	benign	-0.119	Destabilizing	0.949	D	0.436	neutral	None	None	None	None	N
R/K	0.0732	likely_benign	0.0717	benign	-0.601	Destabilizing	0.525	D	0.473	neutral	None	None	None	None	N
R/L	0.1827	likely_benign	0.1676	benign	-0.119	Destabilizing	0.911	D	0.475	neutral	N	0.519326951	None	None	N
R/M	0.1772	likely_benign	0.1655	benign	-0.22	Destabilizing	0.991	D	0.482	neutral	None	None	None	None	N
R/N	0.4144	ambiguous	0.3978	ambiguous	-0.067	Destabilizing	0.842	D	0.467	neutral	None	None	None	None	N
R/P	0.3764	ambiguous	0.3839	ambiguous	-0.271	Destabilizing	0.986	D	0.454	neutral	N	0.445522625	None	None	N
R/Q	0.0861	likely_benign	0.0841	benign	-0.367	Destabilizing	0.067	N	0.281	neutral	None	None	None	None	N
R/S	0.3529	ambiguous	0.3283	benign	-0.727	Destabilizing	0.679	D	0.47	neutral	N	0.458278492	None	None	N
R/T	0.1344	likely_benign	0.1287	benign	-0.535	Destabilizing	0.029	N	0.225	neutral	None	None	None	None	N
R/V	0.2311	likely_benign	0.2157	benign	-0.271	Destabilizing	0.842	D	0.493	neutral	None	None	None	None	N
R/W	0.2109	likely_benign	0.1931	benign	-0.729	Destabilizing	0.998	D	0.445	neutral	None	None	None	None	N
R/Y	0.2935	likely_benign	0.2906	benign	-0.364	Destabilizing	0.991	D	0.459	neutral	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.