TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8479	25660;25661;25662	chr2:178717299;178717298;178717297	chr2:179582026;179582025;179582024
N2AB	8162	24709;24710;24711	chr2:178717299;178717298;178717297	chr2:179582026;179582025;179582024
N2A	7235	21928;21929;21930	chr2:178717299;178717298;178717297	chr2:179582026;179582025;179582024
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: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-70
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1218
• 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	rs990182590	None	None	D	0.387	0.149	0.303123707472	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	3.28947E-03	0	0	None	0	0	0	0	0
V/I	rs990182590	None	None	D	0.387	0.149	0.303123707472	gnomAD-4.0.0	1.97148E-05	None	None	None	None	N	None	0	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	0.8196	likely_pathogenic	0.746	pathogenic	-2.138	Highly Destabilizing	0.51	D	0.661	neutral	N	0.521832191	None	None	N
V/C	0.9737	likely_pathogenic	0.9627	pathogenic	-1.749	Destabilizing	0.998	D	0.749	deleterious	None	None	None	None	N
V/D	0.9983	likely_pathogenic	0.9972	pathogenic	-2.97	Highly Destabilizing	0.999	D	0.822	deleterious	None	None	None	None	N
V/E	0.9934	likely_pathogenic	0.991	pathogenic	-2.834	Highly Destabilizing	0.995	D	0.783	deleterious	D	0.585300943	None	None	N
V/F	0.694	likely_pathogenic	0.6897	pathogenic	-1.393	Destabilizing	0.187	N	0.495	neutral	None	None	None	None	N
V/G	0.9504	likely_pathogenic	0.9131	pathogenic	-2.598	Highly Destabilizing	0.944	D	0.783	deleterious	D	0.591105059	None	None	N
V/H	0.9968	likely_pathogenic	0.9957	pathogenic	-2.307	Highly Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
V/I	0.0844	likely_benign	0.0866	benign	-0.878	Destabilizing	None	N	0.387	neutral	D	0.536105423	None	None	N
V/K	0.9947	likely_pathogenic	0.9931	pathogenic	-1.865	Destabilizing	0.998	D	0.786	deleterious	None	None	None	None	N
V/L	0.55	ambiguous	0.5283	ambiguous	-0.878	Destabilizing	0.125	N	0.498	neutral	D	0.571644307	None	None	N
V/M	0.5066	ambiguous	0.5488	ambiguous	-0.798	Destabilizing	0.672	D	0.417	neutral	None	None	None	None	N
V/N	0.9927	likely_pathogenic	0.9893	pathogenic	-2.038	Highly Destabilizing	0.989	D	0.823	deleterious	None	None	None	None	N
V/P	0.9958	likely_pathogenic	0.9925	pathogenic	-1.271	Destabilizing	0.995	D	0.801	deleterious	None	None	None	None	N
V/Q	0.9888	likely_pathogenic	0.9862	pathogenic	-2.018	Highly Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	N
V/R	0.9893	likely_pathogenic	0.9855	pathogenic	-1.497	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
V/S	0.9585	likely_pathogenic	0.9351	pathogenic	-2.568	Highly Destabilizing	0.376	N	0.521	neutral	None	None	None	None	N
V/T	0.8922	likely_pathogenic	0.8524	pathogenic	-2.313	Highly Destabilizing	0.574	D	0.68	prob.neutral	None	None	None	None	N
V/W	0.9962	likely_pathogenic	0.9952	pathogenic	-1.895	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
V/Y	0.9804	likely_pathogenic	0.9762	pathogenic	-1.582	Destabilizing	0.956	D	0.789	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.