TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5925	17998;17999;18000	chr2:178730760;178730759;178730758	chr2:179595487;179595486;179595485
N2AB	5608	17047;17048;17049	chr2:178730760;178730759;178730758	chr2:179595487;179595486;179595485
N2A	4681	14266;14267;14268	chr2:178730760;178730759;178730758	chr2:179595487;179595486;179595485
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: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-43
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.2618
• 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/M	rs750909367	None	1.0	N	0.747	0.268	0.390531646278	gnomAD-4.0.0	6.87957E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.03896E-07	0	0
L/V	rs750909367	-1.37	0.999	N	0.506	0.292	0.322786055943	gnomAD-2.1.1	4.1E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.11E-06	0
L/V	rs750909367	-1.37	0.999	N	0.506	0.292	0.322786055943	gnomAD-4.0.0	8.94344E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.08468E-05	0	1.66539E-05

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	0.9514	likely_pathogenic	0.9584	pathogenic	-2.313	Highly Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
L/C	0.9776	likely_pathogenic	0.9815	pathogenic	-1.527	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
L/D	0.9988	likely_pathogenic	0.999	pathogenic	-1.985	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
L/E	0.9922	likely_pathogenic	0.9938	pathogenic	-1.88	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
L/F	0.8709	likely_pathogenic	0.8874	pathogenic	-1.482	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
L/G	0.9894	likely_pathogenic	0.9904	pathogenic	-2.767	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/H	0.9909	likely_pathogenic	0.9926	pathogenic	-2.043	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/I	0.3928	ambiguous	0.4365	ambiguous	-1.06	Destabilizing	0.999	D	0.53	neutral	None	None	None	None	N
L/K	0.9887	likely_pathogenic	0.9907	pathogenic	-1.607	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
L/M	0.4422	ambiguous	0.4946	ambiguous	-0.859	Destabilizing	1.0	D	0.747	deleterious	N	0.477638392	None	None	N
L/N	0.9915	likely_pathogenic	0.992	pathogenic	-1.552	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
L/P	0.7778	likely_pathogenic	0.7684	pathogenic	-1.453	Destabilizing	1.0	D	0.862	deleterious	N	0.498959173	None	None	N
L/Q	0.9722	likely_pathogenic	0.9767	pathogenic	-1.611	Destabilizing	1.0	D	0.865	deleterious	N	0.515746233	None	None	N
L/R	0.9803	likely_pathogenic	0.9836	pathogenic	-1.135	Destabilizing	1.0	D	0.875	deleterious	N	0.509162867	None	None	N
L/S	0.9939	likely_pathogenic	0.9949	pathogenic	-2.285	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
L/T	0.971	likely_pathogenic	0.9754	pathogenic	-2.048	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/V	0.5209	ambiguous	0.5619	ambiguous	-1.453	Destabilizing	0.999	D	0.506	neutral	N	0.488234229	None	None	N
L/W	0.9784	likely_pathogenic	0.981	pathogenic	-1.678	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
L/Y	0.9892	likely_pathogenic	0.9914	pathogenic	-1.462	Destabilizing	1.0	D	0.843	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.