TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30383	91372;91373;91374	chr2:178551753;178551752;178551751	chr2:179416480;179416479;179416478
N2AB	28742	86449;86450;86451	chr2:178551753;178551752;178551751	chr2:179416480;179416479;179416478
N2A	27815	83668;83669;83670	chr2:178551753;178551752;178551751	chr2:179416480;179416479;179416478
N2B	21318	64177;64178;64179	chr2:178551753;178551752;178551751	chr2:179416480;179416479;179416478
Novex-1	21443	64552;64553;64554	chr2:178551753;178551752;178551751	chr2:179416480;179416479;179416478
Novex-2	21510	64753;64754;64755	chr2:178551753;178551752;178551751	chr2:179416480;179416479;179416478
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: Fn3-109
• Domain position: 60
• Structural Position: 90
• Q(SASA): 0.57
• 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/Q	rs749647536	-0.194	1.0	N	0.671	0.241	0.372087925617	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
E/Q	rs749647536	-0.194	1.0	N	0.671	0.241	0.372087925617	gnomAD-4.0.0	1.3684E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79893E-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	0.2645	likely_benign	0.3099	benign	-0.516	Destabilizing	0.999	D	0.673	neutral	N	0.505589649	None	None	N
E/C	0.8647	likely_pathogenic	0.8815	pathogenic	-0.374	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/D	0.1495	likely_benign	0.1625	benign	-0.677	Destabilizing	0.999	D	0.527	neutral	N	0.511747617	None	None	N
E/F	0.8056	likely_pathogenic	0.8322	pathogenic	0.249	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/G	0.317	likely_benign	0.3977	ambiguous	-0.849	Destabilizing	1.0	D	0.679	prob.neutral	N	0.469331323	None	None	N
E/H	0.5931	likely_pathogenic	0.6331	pathogenic	0.41	Stabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
E/I	0.4226	ambiguous	0.4725	ambiguous	0.381	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/K	0.3814	ambiguous	0.4541	ambiguous	0.025	Stabilizing	0.999	D	0.617	neutral	N	0.497316883	None	None	N
E/L	0.5673	likely_pathogenic	0.628	pathogenic	0.381	Stabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
E/M	0.5602	ambiguous	0.6133	pathogenic	0.463	Stabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
E/N	0.3216	likely_benign	0.3702	ambiguous	-0.734	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
E/P	0.9444	likely_pathogenic	0.9627	pathogenic	0.104	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
E/Q	0.208	likely_benign	0.2338	benign	-0.583	Destabilizing	1.0	D	0.671	neutral	N	0.502896061	None	None	N
E/R	0.5272	ambiguous	0.5864	pathogenic	0.438	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
E/S	0.2714	likely_benign	0.3072	benign	-0.937	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
E/T	0.2863	likely_benign	0.3209	benign	-0.64	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
E/V	0.2812	likely_benign	0.3206	benign	0.104	Stabilizing	1.0	D	0.718	prob.delet.	N	0.519116307	None	None	N
E/W	0.9343	likely_pathogenic	0.9453	pathogenic	0.578	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/Y	0.6867	likely_pathogenic	0.7288	pathogenic	0.546	Stabilizing	1.0	D	0.76	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.