TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15113	45562;45563;45564	chr2:178621487;178621486;178621485	chr2:179486214;179486213;179486212
N2AB	13472	40639;40640;40641	chr2:178621487;178621486;178621485	chr2:179486214;179486213;179486212
N2A	12545	37858;37859;37860	chr2:178621487;178621486;178621485	chr2:179486214;179486213;179486212
N2B	6048	18367;18368;18369	chr2:178621487;178621486;178621485	chr2:179486214;179486213;179486212
Novex-1	6173	18742;18743;18744	chr2:178621487;178621486;178621485	chr2:179486214;179486213;179486212
Novex-2	6240	18943;18944;18945	chr2:178621487;178621486;178621485	chr2:179486214;179486213;179486212
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: Ig-102
• Domain position: 83
• Structural Position: 174
• Q(SASA): 0.1307
• 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/A	rs794729437	-2.22	0.165	N	0.475	0.297	0.452072420954	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
V/A	rs794729437	-2.22	0.165	N	0.475	0.297	0.452072420954	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/A	rs794729437	-2.22	0.165	N	0.475	0.297	0.452072420954	gnomAD-4.0.0	3.85094E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.19193E-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
V/A	0.7103	likely_pathogenic	0.6461	pathogenic	-2.115	Highly Destabilizing	0.165	N	0.475	neutral	N	0.507405094	None	None	N
V/C	0.9271	likely_pathogenic	0.9502	pathogenic	-1.755	Destabilizing	0.981	D	0.626	neutral	None	None	None	None	N
V/D	0.9943	likely_pathogenic	0.9864	pathogenic	-2.937	Highly Destabilizing	0.912	D	0.692	prob.neutral	D	0.591736491	None	None	N
V/E	0.9827	likely_pathogenic	0.9639	pathogenic	-2.696	Highly Destabilizing	0.818	D	0.659	neutral	None	None	None	None	N
V/F	0.6166	likely_pathogenic	0.6732	pathogenic	-1.231	Destabilizing	0.001	N	0.391	neutral	N	0.504986905	None	None	N
V/G	0.8015	likely_pathogenic	0.6877	pathogenic	-2.681	Highly Destabilizing	0.492	N	0.663	neutral	D	0.536517401	None	None	N
V/H	0.995	likely_pathogenic	0.9932	pathogenic	-2.553	Highly Destabilizing	0.981	D	0.675	prob.neutral	None	None	None	None	N
V/I	0.1008	likely_benign	0.1186	benign	-0.521	Destabilizing	0.041	N	0.363	neutral	N	0.498555064	None	None	N
V/K	0.9889	likely_pathogenic	0.9786	pathogenic	-1.857	Destabilizing	0.563	D	0.642	neutral	None	None	None	None	N
V/L	0.2882	likely_benign	0.3837	ambiguous	-0.521	Destabilizing	None	N	0.249	neutral	N	0.363228153	None	None	N
V/M	0.4395	ambiguous	0.4903	ambiguous	-0.639	Destabilizing	0.69	D	0.651	neutral	None	None	None	None	N
V/N	0.9812	likely_pathogenic	0.9663	pathogenic	-2.251	Highly Destabilizing	0.932	D	0.698	prob.neutral	None	None	None	None	N
V/P	0.9907	likely_pathogenic	0.9891	pathogenic	-1.026	Destabilizing	0.932	D	0.65	neutral	None	None	None	None	N
V/Q	0.9825	likely_pathogenic	0.9687	pathogenic	-2.046	Highly Destabilizing	0.932	D	0.653	neutral	None	None	None	None	N
V/R	0.9823	likely_pathogenic	0.9662	pathogenic	-1.739	Destabilizing	0.818	D	0.694	prob.neutral	None	None	None	None	N
V/S	0.9452	likely_pathogenic	0.9097	pathogenic	-2.846	Highly Destabilizing	0.563	D	0.621	neutral	None	None	None	None	N
V/T	0.8606	likely_pathogenic	0.8075	pathogenic	-2.457	Highly Destabilizing	0.388	N	0.603	neutral	None	None	None	None	N
V/W	0.9902	likely_pathogenic	0.9906	pathogenic	-1.837	Destabilizing	0.981	D	0.671	neutral	None	None	None	None	N
V/Y	0.9662	likely_pathogenic	0.9642	pathogenic	-1.437	Destabilizing	0.241	N	0.608	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.