TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26324	79195;79196;79197	chr2:178567162;178567161;178567160	chr2:179431889;179431888;179431887
N2AB	24683	74272;74273;74274	chr2:178567162;178567161;178567160	chr2:179431889;179431888;179431887
N2A	23756	71491;71492;71493	chr2:178567162;178567161;178567160	chr2:179431889;179431888;179431887
N2B	17259	52000;52001;52002	chr2:178567162;178567161;178567160	chr2:179431889;179431888;179431887
Novex-1	17384	52375;52376;52377	chr2:178567162;178567161;178567160	chr2:179431889;179431888;179431887
Novex-2	17451	52576;52577;52578	chr2:178567162;178567161;178567160	chr2:179431889;179431888;179431887
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-79
• Domain position: 39
• Structural Position: 40
• Q(SASA): 0.0987
• 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
V/I	rs747655927	-0.716	0.006	N	0.153	0.073	0.386721274199	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
V/I	rs747655927	-0.716	0.006	N	0.153	0.073	0.386721274199	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/I	rs747655927	-0.716	0.006	N	0.153	0.073	0.386721274199	gnomAD-4.0.0	6.57358E-06	None	None	None	None	N	None	2.41336E-05	0	None	0	0	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
V/A	0.7517	likely_pathogenic	0.7634	pathogenic	-2.39	Highly Destabilizing	0.656	D	0.57	neutral	D	0.533577221	None	None	N
V/C	0.966	likely_pathogenic	0.9703	pathogenic	-1.928	Destabilizing	0.998	D	0.777	deleterious	None	None	None	None	N
V/D	0.9992	likely_pathogenic	0.9993	pathogenic	-3.473	Highly Destabilizing	0.99	D	0.865	deleterious	D	0.560835736	None	None	N
V/E	0.9971	likely_pathogenic	0.9971	pathogenic	-3.15	Highly Destabilizing	0.978	D	0.804	deleterious	None	None	None	None	N
V/F	0.9133	likely_pathogenic	0.9335	pathogenic	-1.384	Destabilizing	0.942	D	0.709	prob.delet.	D	0.560582246	None	None	N
V/G	0.9575	likely_pathogenic	0.9578	pathogenic	-3.015	Highly Destabilizing	0.97	D	0.832	deleterious	D	0.560835736	None	None	N
V/H	0.9991	likely_pathogenic	0.9993	pathogenic	-2.927	Highly Destabilizing	0.998	D	0.869	deleterious	None	None	None	None	N
V/I	0.0776	likely_benign	0.0792	benign	-0.574	Destabilizing	0.006	N	0.153	neutral	N	0.455339761	None	None	N
V/K	0.9978	likely_pathogenic	0.9981	pathogenic	-2.097	Highly Destabilizing	0.978	D	0.807	deleterious	None	None	None	None	N
V/L	0.4848	ambiguous	0.5212	ambiguous	-0.574	Destabilizing	0.006	N	0.295	neutral	N	0.506099442	None	None	N
V/M	0.6837	likely_pathogenic	0.7376	pathogenic	-0.792	Destabilizing	0.956	D	0.629	neutral	None	None	None	None	N
V/N	0.9975	likely_pathogenic	0.9978	pathogenic	-2.788	Highly Destabilizing	0.993	D	0.869	deleterious	None	None	None	None	N
V/P	0.9952	likely_pathogenic	0.9941	pathogenic	-1.159	Destabilizing	0.993	D	0.843	deleterious	None	None	None	None	N
V/Q	0.9964	likely_pathogenic	0.9968	pathogenic	-2.434	Highly Destabilizing	0.993	D	0.865	deleterious	None	None	None	None	N
V/R	0.9955	likely_pathogenic	0.9958	pathogenic	-2.15	Highly Destabilizing	0.978	D	0.868	deleterious	None	None	None	None	N
V/S	0.9762	likely_pathogenic	0.9787	pathogenic	-3.323	Highly Destabilizing	0.978	D	0.761	deleterious	None	None	None	None	N
V/T	0.8592	likely_pathogenic	0.8674	pathogenic	-2.836	Highly Destabilizing	0.86	D	0.583	neutral	None	None	None	None	N
V/W	0.9986	likely_pathogenic	0.9989	pathogenic	-2.006	Highly Destabilizing	0.998	D	0.849	deleterious	None	None	None	None	N
V/Y	0.9957	likely_pathogenic	0.9964	pathogenic	-1.645	Destabilizing	0.978	D	0.739	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.