TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24859	74800;74801;74802	chr2:178571557;178571556;178571555	chr2:179436284;179436283;179436282
N2AB	23218	69877;69878;69879	chr2:178571557;178571556;178571555	chr2:179436284;179436283;179436282
N2A	22291	67096;67097;67098	chr2:178571557;178571556;178571555	chr2:179436284;179436283;179436282
N2B	15794	47605;47606;47607	chr2:178571557;178571556;178571555	chr2:179436284;179436283;179436282
Novex-1	15919	47980;47981;47982	chr2:178571557;178571556;178571555	chr2:179436284;179436283;179436282
Novex-2	15986	48181;48182;48183	chr2:178571557;178571556;178571555	chr2:179436284;179436283;179436282
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: Fn3-68
• Domain position: 52
• Structural Position: 68
• Q(SASA): 0.2581
• 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/L	rs773227508	-0.443	0.039	N	0.271	0.169	0.4744847356	gnomAD-2.1.1	4.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.97E-06	0
V/L	rs773227508	-0.443	0.039	N	0.271	0.169	0.4744847356	gnomAD-4.0.0	6.37002E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.14384E-05	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	0.7575	likely_pathogenic	0.7703	pathogenic	-1.183	Destabilizing	0.928	D	0.471	neutral	N	0.514825208	None	None	I
V/C	0.9386	likely_pathogenic	0.9425	pathogenic	-0.985	Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	I
V/D	0.9899	likely_pathogenic	0.9913	pathogenic	-0.58	Destabilizing	0.997	D	0.849	deleterious	None	None	None	None	I
V/E	0.962	likely_pathogenic	0.9673	pathogenic	-0.533	Destabilizing	0.989	D	0.804	deleterious	N	0.490042471	None	None	I
V/F	0.7108	likely_pathogenic	0.7269	pathogenic	-0.746	Destabilizing	0.968	D	0.815	deleterious	None	None	None	None	I
V/G	0.9432	likely_pathogenic	0.9483	pathogenic	-1.537	Destabilizing	0.989	D	0.805	deleterious	N	0.514440603	None	None	I
V/H	0.9873	likely_pathogenic	0.9889	pathogenic	-1.014	Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	I
V/I	0.0765	likely_benign	0.0754	benign	-0.306	Destabilizing	0.726	D	0.441	neutral	N	0.512246263	None	None	I
V/K	0.9793	likely_pathogenic	0.9829	pathogenic	-0.973	Destabilizing	0.992	D	0.805	deleterious	None	None	None	None	I
V/L	0.3757	ambiguous	0.397	ambiguous	-0.306	Destabilizing	0.039	N	0.271	neutral	N	0.50624301	None	None	I
V/M	0.4705	ambiguous	0.5029	ambiguous	-0.382	Destabilizing	0.983	D	0.714	prob.delet.	None	None	None	None	I
V/N	0.9667	likely_pathogenic	0.9715	pathogenic	-0.93	Destabilizing	0.997	D	0.843	deleterious	None	None	None	None	I
V/P	0.9871	likely_pathogenic	0.9877	pathogenic	-0.562	Destabilizing	0.997	D	0.832	deleterious	None	None	None	None	I
V/Q	0.9564	likely_pathogenic	0.9623	pathogenic	-0.955	Destabilizing	0.997	D	0.834	deleterious	None	None	None	None	I
V/R	0.9704	likely_pathogenic	0.9741	pathogenic	-0.638	Destabilizing	0.992	D	0.843	deleterious	None	None	None	None	I
V/S	0.9078	likely_pathogenic	0.9173	pathogenic	-1.543	Destabilizing	0.992	D	0.787	deleterious	None	None	None	None	I
V/T	0.779	likely_pathogenic	0.8008	pathogenic	-1.36	Destabilizing	0.944	D	0.52	neutral	None	None	None	None	I
V/W	0.9934	likely_pathogenic	0.9937	pathogenic	-0.966	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	I
V/Y	0.9687	likely_pathogenic	0.971	pathogenic	-0.624	Destabilizing	0.992	D	0.824	deleterious	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.