TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6687	20284;20285;20286	chr2:178727306;178727305;178727304	chr2:179592033;179592032;179592031
N2AB	6370	19333;19334;19335	chr2:178727306;178727305;178727304	chr2:179592033;179592032;179592031
N2A	5443	16552;16553;16554	chr2:178727306;178727305;178727304	chr2:179592033;179592032;179592031
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-51
• Domain position: 21
• Structural Position: 30
• Q(SASA): 0.2418
• 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/V	rs2079507159	None	0.977	D	0.689	0.626	0.524792858863	gnomAD-4.0.0	1.36953E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79988E-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	0.7617	likely_pathogenic	0.7495	pathogenic	-2.855	Highly Destabilizing	0.966	D	0.723	prob.delet.	None	None	None	None	N
L/C	0.804	likely_pathogenic	0.7944	pathogenic	-1.999	Destabilizing	0.483	N	0.56	neutral	None	None	None	None	N
L/D	0.9912	likely_pathogenic	0.9908	pathogenic	-3.371	Highly Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
L/E	0.9416	likely_pathogenic	0.9407	pathogenic	-3.126	Highly Destabilizing	0.999	D	0.872	deleterious	None	None	None	None	N
L/F	0.0982	likely_benign	0.0938	benign	-1.78	Destabilizing	0.999	D	0.818	deleterious	N	0.492135641	None	None	N
L/G	0.9462	likely_pathogenic	0.9453	pathogenic	-3.389	Highly Destabilizing	0.998	D	0.891	deleterious	None	None	None	None	N
L/H	0.7545	likely_pathogenic	0.7382	pathogenic	-2.646	Highly Destabilizing	1.0	D	0.865	deleterious	D	0.622184762	None	None	N
L/I	0.1647	likely_benign	0.1493	benign	-1.285	Destabilizing	0.977	D	0.652	neutral	D	0.544481043	None	None	N
L/K	0.9303	likely_pathogenic	0.9269	pathogenic	-2.359	Highly Destabilizing	0.999	D	0.875	deleterious	None	None	None	None	N
L/M	0.1707	likely_benign	0.1539	benign	-1.123	Destabilizing	0.999	D	0.756	deleterious	None	None	None	None	N
L/N	0.9577	likely_pathogenic	0.9536	pathogenic	-2.761	Highly Destabilizing	0.999	D	0.889	deleterious	None	None	None	None	N
L/P	0.9847	likely_pathogenic	0.9862	pathogenic	-1.794	Destabilizing	0.999	D	0.889	deleterious	D	0.605933236	None	None	N
L/Q	0.752	likely_pathogenic	0.7323	pathogenic	-2.644	Highly Destabilizing	0.999	D	0.867	deleterious	None	None	None	None	N
L/R	0.8585	likely_pathogenic	0.8614	pathogenic	-1.995	Destabilizing	0.999	D	0.859	deleterious	D	0.622184762	None	None	N
L/S	0.9135	likely_pathogenic	0.9033	pathogenic	-3.41	Highly Destabilizing	0.995	D	0.878	deleterious	None	None	None	None	N
L/T	0.8182	likely_pathogenic	0.7989	pathogenic	-3.021	Highly Destabilizing	0.995	D	0.824	deleterious	None	None	None	None	N
L/V	0.2023	likely_benign	0.187	benign	-1.794	Destabilizing	0.977	D	0.689	prob.neutral	D	0.567545706	None	None	N
L/W	0.3385	likely_benign	0.3433	ambiguous	-2.121	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
L/Y	0.4176	ambiguous	0.4257	ambiguous	-1.87	Destabilizing	0.999	D	0.804	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.