TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20619	62080;62081;62082	chr2:178589870;178589869;178589868	chr2:179454597;179454596;179454595
N2AB	18978	57157;57158;57159	chr2:178589870;178589869;178589868	chr2:179454597;179454596;179454595
N2A	18051	54376;54377;54378	chr2:178589870;178589869;178589868	chr2:179454597;179454596;179454595
N2B	11554	34885;34886;34887	chr2:178589870;178589869;178589868	chr2:179454597;179454596;179454595
Novex-1	11679	35260;35261;35262	chr2:178589870;178589869;178589868	chr2:179454597;179454596;179454595
Novex-2	11746	35461;35462;35463	chr2:178589870;178589869;178589868	chr2:179454597;179454596;179454595
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: Fn3-37
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.2707
• Predicted PPI site: I

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/F	rs1377163743	None	0.497	N	0.69	0.208	0.546435761033	gnomAD-4.0.0	1.59211E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	2.41313E-04	0	0	0
V/L	None	None	0.009	N	0.369	0.093	0.318828661733	gnomAD-4.0.0	1.59211E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43308E-05	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	0.5467	ambiguous	0.4914	ambiguous	-1.206	Destabilizing	0.104	N	0.503	neutral	D	0.523828693	None	None	I
V/C	0.9	likely_pathogenic	0.8729	pathogenic	-0.815	Destabilizing	0.968	D	0.676	prob.neutral	None	None	None	None	I
V/D	0.9851	likely_pathogenic	0.9679	pathogenic	-0.905	Destabilizing	0.667	D	0.77	deleterious	D	0.522261282	None	None	I
V/E	0.9585	likely_pathogenic	0.927	pathogenic	-0.796	Destabilizing	0.726	D	0.728	prob.delet.	None	None	None	None	I
V/F	0.5902	likely_pathogenic	0.5018	ambiguous	-0.664	Destabilizing	0.497	N	0.69	prob.neutral	N	0.491434823	None	None	I
V/G	0.8605	likely_pathogenic	0.778	pathogenic	-1.622	Destabilizing	0.667	D	0.743	deleterious	N	0.501158513	None	None	I
V/H	0.9811	likely_pathogenic	0.9644	pathogenic	-1.227	Destabilizing	0.968	D	0.749	deleterious	None	None	None	None	I
V/I	0.0941	likely_benign	0.0981	benign	-0.127	Destabilizing	None	N	0.218	neutral	N	0.500682475	None	None	I
V/K	0.9672	likely_pathogenic	0.9412	pathogenic	-0.983	Destabilizing	0.726	D	0.733	prob.delet.	None	None	None	None	I
V/L	0.414	ambiguous	0.3802	ambiguous	-0.127	Destabilizing	0.009	N	0.369	neutral	N	0.467810386	None	None	I
V/M	0.4416	ambiguous	0.4015	ambiguous	-0.18	Destabilizing	0.567	D	0.59	neutral	None	None	None	None	I
V/N	0.9566	likely_pathogenic	0.9257	pathogenic	-1.048	Destabilizing	0.89	D	0.766	deleterious	None	None	None	None	I
V/P	0.9581	likely_pathogenic	0.9272	pathogenic	-0.452	Destabilizing	0.89	D	0.736	prob.delet.	None	None	None	None	I
V/Q	0.9446	likely_pathogenic	0.9077	pathogenic	-0.994	Destabilizing	0.89	D	0.733	prob.delet.	None	None	None	None	I
V/R	0.9487	likely_pathogenic	0.9127	pathogenic	-0.763	Destabilizing	0.726	D	0.763	deleterious	None	None	None	None	I
V/S	0.8374	likely_pathogenic	0.7574	pathogenic	-1.659	Destabilizing	0.726	D	0.671	neutral	None	None	None	None	I
V/T	0.5981	likely_pathogenic	0.5291	ambiguous	-1.412	Destabilizing	0.272	N	0.508	neutral	None	None	None	None	I
V/W	0.9879	likely_pathogenic	0.9788	pathogenic	-1.021	Destabilizing	0.968	D	0.722	prob.delet.	None	None	None	None	I
V/Y	0.9484	likely_pathogenic	0.923	pathogenic	-0.608	Destabilizing	0.726	D	0.699	prob.neutral	None	None	None	None	I

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.