TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1897	5914;5915;5916	chr2:178776175;178776174;178776173	chr2:179640902;179640901;179640900
N2AB	1897	5914;5915;5916	chr2:178776175;178776174;178776173	chr2:179640902;179640901;179640900
N2A	1897	5914;5915;5916	chr2:178776175;178776174;178776173	chr2:179640902;179640901;179640900
N2B	1851	5776;5777;5778	chr2:178776175;178776174;178776173	chr2:179640902;179640901;179640900
Novex-1	1851	5776;5777;5778	chr2:178776175;178776174;178776173	chr2:179640902;179640901;179640900
Novex-2	1851	5776;5777;5778	chr2:178776175;178776174;178776173	chr2:179640902;179640901;179640900
Novex-3	1897	5914;5915;5916	chr2:178776175;178776174;178776173	chr2:179640902;179640901;179640900

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-9
• Domain position: 57
• Structural Position: 138
• Q(SASA): 0.0731
• 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/Q	rs1299766514	-2.207	1.0	D	0.902	0.69	0.896200649061	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	2.89E-05	None	0	0	None	0	None	0	0	0
L/Q	rs1299766514	-2.207	1.0	D	0.902	0.69	0.896200649061	gnomAD-4.0.0	1.5905E-06	None	None	None	None	N	None	0	2.28634E-05	None	0	0	None	0	0	0	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	0.959	likely_pathogenic	0.9633	pathogenic	-2.708	Highly Destabilizing	0.999	D	0.742	deleterious	None	None	None	None	N
L/C	0.903	likely_pathogenic	0.9166	pathogenic	-1.776	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/D	0.9999	likely_pathogenic	0.9999	pathogenic	-3.367	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
L/E	0.9989	likely_pathogenic	0.9989	pathogenic	-3.037	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
L/F	0.5	ambiguous	0.5089	ambiguous	-1.694	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
L/G	0.9953	likely_pathogenic	0.9956	pathogenic	-3.327	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
L/H	0.9961	likely_pathogenic	0.9962	pathogenic	-3.063	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
L/I	0.3476	ambiguous	0.3607	ambiguous	-0.843	Destabilizing	0.999	D	0.63	neutral	None	None	None	None	N
L/K	0.9984	likely_pathogenic	0.9983	pathogenic	-2.063	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
L/M	0.3149	likely_benign	0.3209	benign	-0.908	Destabilizing	1.0	D	0.786	deleterious	D	0.643615413	None	None	N
L/N	0.999	likely_pathogenic	0.999	pathogenic	-2.792	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
L/P	0.9995	likely_pathogenic	0.9995	pathogenic	-1.456	Destabilizing	1.0	D	0.899	deleterious	D	0.717090994	None	None	N
L/Q	0.9938	likely_pathogenic	0.994	pathogenic	-2.422	Highly Destabilizing	1.0	D	0.902	deleterious	D	0.774256312	None	None	N
L/R	0.9953	likely_pathogenic	0.9951	pathogenic	-2.152	Highly Destabilizing	1.0	D	0.895	deleterious	D	0.717090994	None	None	N
L/S	0.9972	likely_pathogenic	0.9974	pathogenic	-3.355	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
L/T	0.9776	likely_pathogenic	0.9796	pathogenic	-2.855	Highly Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
L/V	0.3829	ambiguous	0.4103	ambiguous	-1.456	Destabilizing	0.999	D	0.637	neutral	D	0.653455833	None	None	N
L/W	0.9788	likely_pathogenic	0.9797	pathogenic	-2.122	Highly Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
L/Y	0.9841	likely_pathogenic	0.9843	pathogenic	-1.875	Destabilizing	1.0	D	0.854	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.