TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6086	18481;18482;18483	chr2:178730144;178730143;178730142	chr2:179594871;179594870;179594869
N2AB	5769	17530;17531;17532	chr2:178730144;178730143;178730142	chr2:179594871;179594870;179594869
N2A	4842	14749;14750;14751	chr2:178730144;178730143;178730142	chr2:179594871;179594870;179594869
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-44
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.0915
• 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
L/I	rs1160746683	-1.161	0.002	N	0.284	0.126	0.226586394389	gnomAD-2.1.1	1.21E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.67E-05	0
L/I	rs1160746683	-1.161	0.002	N	0.284	0.126	0.226586394389	gnomAD-4.0.0	3.18523E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86022E-06	1.43394E-05	0
L/V	None	None	0.022	N	0.292	0.189	0.18274738541	gnomAD-4.0.0	1.59262E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86022E-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
L/A	0.5372	ambiguous	0.5435	ambiguous	-2.602	Highly Destabilizing	0.029	N	0.485	neutral	None	None	None	None	N
L/C	0.7427	likely_pathogenic	0.7433	pathogenic	-2.325	Highly Destabilizing	0.991	D	0.788	deleterious	None	None	None	None	N
L/D	0.996	likely_pathogenic	0.9968	pathogenic	-3.429	Highly Destabilizing	0.974	D	0.821	deleterious	None	None	None	None	N
L/E	0.9801	likely_pathogenic	0.9838	pathogenic	-3.23	Highly Destabilizing	0.974	D	0.802	deleterious	None	None	None	None	N
L/F	0.4801	ambiguous	0.5254	ambiguous	-1.454	Destabilizing	0.949	D	0.734	prob.delet.	None	None	None	None	N
L/G	0.9217	likely_pathogenic	0.9305	pathogenic	-3.092	Highly Destabilizing	0.842	D	0.779	deleterious	None	None	None	None	N
L/H	0.9422	likely_pathogenic	0.9564	pathogenic	-2.477	Highly Destabilizing	0.998	D	0.823	deleterious	None	None	None	None	N
L/I	0.0723	likely_benign	0.072	benign	-1.183	Destabilizing	0.002	N	0.284	neutral	N	0.392278078	None	None	N
L/K	0.9752	likely_pathogenic	0.9808	pathogenic	-1.965	Destabilizing	0.974	D	0.787	deleterious	None	None	None	None	N
L/M	0.2265	likely_benign	0.23	benign	-1.457	Destabilizing	0.949	D	0.694	prob.neutral	None	None	None	None	N
L/N	0.9674	likely_pathogenic	0.9734	pathogenic	-2.371	Highly Destabilizing	0.991	D	0.831	deleterious	None	None	None	None	N
L/P	0.9881	likely_pathogenic	0.9889	pathogenic	-1.639	Destabilizing	0.966	D	0.828	deleterious	N	0.436743719	None	None	N
L/Q	0.9155	likely_pathogenic	0.9338	pathogenic	-2.273	Highly Destabilizing	0.989	D	0.817	deleterious	N	0.496002666	None	None	N
L/R	0.9444	likely_pathogenic	0.9573	pathogenic	-1.647	Destabilizing	0.966	D	0.813	deleterious	N	0.496002666	None	None	N
L/S	0.8857	likely_pathogenic	0.8999	pathogenic	-2.961	Highly Destabilizing	0.728	D	0.761	deleterious	None	None	None	None	N
L/T	0.7373	likely_pathogenic	0.7488	pathogenic	-2.63	Highly Destabilizing	0.842	D	0.71	prob.delet.	None	None	None	None	N
L/V	0.0858	likely_benign	0.0835	benign	-1.639	Destabilizing	0.022	N	0.292	neutral	N	0.307155107	None	None	N
L/W	0.8966	likely_pathogenic	0.929	pathogenic	-1.849	Destabilizing	0.998	D	0.793	deleterious	None	None	None	None	N
L/Y	0.8908	likely_pathogenic	0.9149	pathogenic	-1.634	Destabilizing	0.991	D	0.795	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.