TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26143	78652;78653;78654	chr2:178567705;178567704;178567703	chr2:179432432;179432431;179432430
N2AB	24502	73729;73730;73731	chr2:178567705;178567704;178567703	chr2:179432432;179432431;179432430
N2A	23575	70948;70949;70950	chr2:178567705;178567704;178567703	chr2:179432432;179432431;179432430
N2B	17078	51457;51458;51459	chr2:178567705;178567704;178567703	chr2:179432432;179432431;179432430
Novex-1	17203	51832;51833;51834	chr2:178567705;178567704;178567703	chr2:179432432;179432431;179432430
Novex-2	17270	52033;52034;52035	chr2:178567705;178567704;178567703	chr2:179432432;179432431;179432430
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-78
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.1122
• 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	None	None	0.006	N	0.208	0.12	0.340510301474	gnomAD-4.0.0	1.59627E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88693E-05	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	0.9016	likely_pathogenic	0.8859	pathogenic	-1.356	Destabilizing	0.656	D	0.53	neutral	N	0.483521557	None	None	N
V/C	0.954	likely_pathogenic	0.9432	pathogenic	-0.885	Destabilizing	0.998	D	0.692	prob.neutral	None	None	None	None	N
V/D	0.9887	likely_pathogenic	0.9857	pathogenic	-1.102	Destabilizing	0.99	D	0.792	deleterious	N	0.495509746	None	None	N
V/E	0.9676	likely_pathogenic	0.9607	pathogenic	-0.888	Destabilizing	0.993	D	0.736	prob.delet.	None	None	None	None	N
V/F	0.858	likely_pathogenic	0.8199	pathogenic	-0.684	Destabilizing	0.942	D	0.695	prob.neutral	N	0.500197462	None	None	N
V/G	0.9487	likely_pathogenic	0.9366	pathogenic	-1.884	Destabilizing	0.97	D	0.765	deleterious	N	0.52165518	None	None	N
V/H	0.9887	likely_pathogenic	0.9854	pathogenic	-1.658	Destabilizing	0.998	D	0.793	deleterious	None	None	None	None	N
V/I	0.0703	likely_benign	0.0661	benign	0.091	Stabilizing	0.006	N	0.208	neutral	N	0.457259772	None	None	N
V/K	0.9729	likely_pathogenic	0.9677	pathogenic	-0.782	Destabilizing	0.978	D	0.738	prob.delet.	None	None	None	None	N
V/L	0.648	likely_pathogenic	0.5909	pathogenic	0.091	Stabilizing	0.125	N	0.407	neutral	D	0.522713973	None	None	N
V/M	0.6213	likely_pathogenic	0.5591	ambiguous	-0.082	Destabilizing	0.956	D	0.647	neutral	None	None	None	None	N
V/N	0.946	likely_pathogenic	0.9349	pathogenic	-1.019	Destabilizing	0.993	D	0.809	deleterious	None	None	None	None	N
V/P	0.9898	likely_pathogenic	0.9875	pathogenic	-0.361	Destabilizing	0.993	D	0.717	prob.delet.	None	None	None	None	N
V/Q	0.9649	likely_pathogenic	0.9573	pathogenic	-0.809	Destabilizing	0.993	D	0.748	deleterious	None	None	None	None	N
V/R	0.9653	likely_pathogenic	0.9582	pathogenic	-0.87	Destabilizing	0.993	D	0.811	deleterious	None	None	None	None	N
V/S	0.9414	likely_pathogenic	0.9313	pathogenic	-1.744	Destabilizing	0.978	D	0.689	prob.neutral	None	None	None	None	N
V/T	0.8778	likely_pathogenic	0.8596	pathogenic	-1.369	Destabilizing	0.86	D	0.607	neutral	None	None	None	None	N
V/W	0.9968	likely_pathogenic	0.9952	pathogenic	-1.116	Destabilizing	0.998	D	0.751	deleterious	None	None	None	None	N
V/Y	0.9819	likely_pathogenic	0.9759	pathogenic	-0.657	Destabilizing	0.978	D	0.699	prob.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.