TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31515	94768;94769;94770	chr2:178546885;178546884;178546883	chr2:179411612;179411611;179411610
N2AB	29874	89845;89846;89847	chr2:178546885;178546884;178546883	chr2:179411612;179411611;179411610
N2A	28947	87064;87065;87066	chr2:178546885;178546884;178546883	chr2:179411612;179411611;179411610
N2B	22450	67573;67574;67575	chr2:178546885;178546884;178546883	chr2:179411612;179411611;179411610
Novex-1	22575	67948;67949;67950	chr2:178546885;178546884;178546883	chr2:179411612;179411611;179411610
Novex-2	22642	68149;68150;68151	chr2:178546885;178546884;178546883	chr2:179411612;179411611;179411610
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-118
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.3091
• 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	None	None	0.998	N	0.644	0.413	0.533904276971	gnomAD-4.0.0	2.78047E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.64544E-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	0.6315	likely_pathogenic	0.586	pathogenic	-1.313	Destabilizing	0.998	D	0.644	neutral	N	0.462550948	None	None	N
V/C	0.9433	likely_pathogenic	0.9422	pathogenic	-1.072	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
V/D	0.9823	likely_pathogenic	0.9823	pathogenic	-0.915	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
V/E	0.9423	likely_pathogenic	0.9436	pathogenic	-0.923	Destabilizing	1.0	D	0.829	deleterious	N	0.512308371	None	None	N
V/F	0.7569	likely_pathogenic	0.779	pathogenic	-1.02	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
V/G	0.8549	likely_pathogenic	0.8373	pathogenic	-1.623	Destabilizing	1.0	D	0.847	deleterious	D	0.522650718	None	None	N
V/H	0.9895	likely_pathogenic	0.9898	pathogenic	-1.102	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
V/I	0.0907	likely_benign	0.0931	benign	-0.574	Destabilizing	0.813	D	0.333	neutral	None	None	None	None	N
V/K	0.966	likely_pathogenic	0.9615	pathogenic	-1.146	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
V/L	0.666	likely_pathogenic	0.6678	pathogenic	-0.574	Destabilizing	0.981	D	0.533	neutral	D	0.526679784	None	None	N
V/M	0.558	ambiguous	0.5452	ambiguous	-0.532	Destabilizing	0.999	D	0.777	deleterious	N	0.504711048	None	None	N
V/N	0.9586	likely_pathogenic	0.9541	pathogenic	-0.935	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/P	0.7176	likely_pathogenic	0.6891	pathogenic	-0.784	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
V/Q	0.9604	likely_pathogenic	0.9584	pathogenic	-1.08	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
V/R	0.9599	likely_pathogenic	0.957	pathogenic	-0.645	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/S	0.9109	likely_pathogenic	0.8943	pathogenic	-1.485	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
V/T	0.8041	likely_pathogenic	0.7743	pathogenic	-1.369	Destabilizing	0.998	D	0.727	prob.delet.	None	None	None	None	N
V/W	0.9905	likely_pathogenic	0.9921	pathogenic	-1.163	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
V/Y	0.955	likely_pathogenic	0.961	pathogenic	-0.878	Destabilizing	1.0	D	0.824	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.