TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4857	14794;14795;14796	chr2:178735877;178735876;178735875	chr2:179600604;179600603;179600602
N2AB	4540	13843;13844;13845	chr2:178735877;178735876;178735875	chr2:179600604;179600603;179600602
N2A	3613	11062;11063;11064	chr2:178735877;178735876;178735875	chr2:179600604;179600603;179600602
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: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-31
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.074
• 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/F	None	None	0.999	N	0.782	0.368	0.707450365078	gnomAD-4.0.0	2.05257E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69833E-06	0	0
L/I	None	None	0.992	N	0.562	0.269	0.555908562551	gnomAD-4.0.0	1.36838E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79889E-06	0	0
L/R	rs1267218460	-1.496	1.0	N	0.782	0.744	0.858254026184	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
L/R	rs1267218460	-1.496	1.0	N	0.782	0.744	0.858254026184	gnomAD-4.0.0	3.18227E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41313E-04	2.85794E-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	0.5653	likely_pathogenic	0.4495	ambiguous	-2.21	Highly Destabilizing	0.997	D	0.617	neutral	None	None	None	None	N
L/C	0.6763	likely_pathogenic	0.603	pathogenic	-2.017	Highly Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
L/D	0.9774	likely_pathogenic	0.9669	pathogenic	-2.05	Highly Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
L/E	0.902	likely_pathogenic	0.8623	pathogenic	-1.97	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
L/F	0.5299	ambiguous	0.427	ambiguous	-1.642	Destabilizing	0.999	D	0.782	deleterious	N	0.512938934	None	None	N
L/G	0.8655	likely_pathogenic	0.8079	pathogenic	-2.596	Highly Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
L/H	0.8173	likely_pathogenic	0.7528	pathogenic	-1.78	Destabilizing	1.0	D	0.739	prob.delet.	D	0.613288247	None	None	N
L/I	0.1159	likely_benign	0.094	benign	-1.167	Destabilizing	0.992	D	0.562	neutral	N	0.457026083	None	None	N
L/K	0.8767	likely_pathogenic	0.8469	pathogenic	-1.53	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
L/M	0.2062	likely_benign	0.1721	benign	-1.209	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
L/N	0.8201	likely_pathogenic	0.7722	pathogenic	-1.572	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
L/P	0.7567	likely_pathogenic	0.7252	pathogenic	-1.49	Destabilizing	1.0	D	0.777	deleterious	N	0.510788487	None	None	N
L/Q	0.6979	likely_pathogenic	0.6243	pathogenic	-1.707	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
L/R	0.787	likely_pathogenic	0.7376	pathogenic	-1.029	Destabilizing	1.0	D	0.782	deleterious	N	0.513961416	None	None	N
L/S	0.7441	likely_pathogenic	0.6272	pathogenic	-2.307	Highly Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
L/T	0.4724	ambiguous	0.3685	ambiguous	-2.1	Highly Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
L/V	0.1205	likely_benign	0.094	benign	-1.49	Destabilizing	0.767	D	0.395	neutral	N	0.37668368	None	None	N
L/W	0.8519	likely_pathogenic	0.7968	pathogenic	-1.732	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
L/Y	0.874	likely_pathogenic	0.8257	pathogenic	-1.484	Destabilizing	1.0	D	0.793	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.