TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29051	87376;87377;87378	chr2:178558203;178558202;178558201	chr2:179422930;179422929;179422928
N2AB	27410	82453;82454;82455	chr2:178558203;178558202;178558201	chr2:179422930;179422929;179422928
N2A	26483	79672;79673;79674	chr2:178558203;178558202;178558201	chr2:179422930;179422929;179422928
N2B	19986	60181;60182;60183	chr2:178558203;178558202;178558201	chr2:179422930;179422929;179422928
Novex-1	20111	60556;60557;60558	chr2:178558203;178558202;178558201	chr2:179422930;179422929;179422928
Novex-2	20178	60757;60758;60759	chr2:178558203;178558202;178558201	chr2:179422930;179422929;179422928
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-145
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.3078
• 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
S/G	rs1702239501	None	0.454	N	0.387	0.096	0.130388298395	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.54E-05	0	0	0	None	0	0	0	0	0
S/G	rs1702239501	None	0.454	N	0.387	0.096	0.130388298395	gnomAD-4.0.0	6.56909E-06	None	None	None	None	N	None	0	6.54279E-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
S/A	0.0764	likely_benign	0.0783	benign	-0.18	Destabilizing	0.688	D	0.407	neutral	None	None	None	None	N
S/C	0.0985	likely_benign	0.0907	benign	-0.277	Destabilizing	0.997	D	0.474	neutral	N	0.462038368	None	None	N
S/D	0.3197	likely_benign	0.2517	benign	-0.059	Destabilizing	0.728	D	0.379	neutral	None	None	None	None	N
S/E	0.4992	ambiguous	0.4057	ambiguous	-0.158	Destabilizing	0.842	D	0.39	neutral	None	None	None	None	N
S/F	0.1984	likely_benign	0.1916	benign	-0.848	Destabilizing	0.974	D	0.555	neutral	None	None	None	None	N
S/G	0.0713	likely_benign	0.0639	benign	-0.261	Destabilizing	0.454	N	0.387	neutral	N	0.390407556	None	None	N
S/H	0.2631	likely_benign	0.1726	benign	-0.602	Destabilizing	0.007	N	0.229	neutral	None	None	None	None	N
S/I	0.1858	likely_benign	0.167	benign	-0.1	Destabilizing	0.966	D	0.549	neutral	N	0.460304785	None	None	N
S/K	0.5673	likely_pathogenic	0.4006	ambiguous	-0.454	Destabilizing	0.842	D	0.388	neutral	None	None	None	None	N
S/L	0.1067	likely_benign	0.1113	benign	-0.1	Destabilizing	0.842	D	0.536	neutral	None	None	None	None	N
S/M	0.1927	likely_benign	0.1813	benign	-0.07	Destabilizing	0.998	D	0.471	neutral	None	None	None	None	N
S/N	0.0995	likely_benign	0.079	benign	-0.16	Destabilizing	0.012	N	0.167	neutral	N	0.405491652	None	None	N
S/P	0.2808	likely_benign	0.2569	benign	-0.1	Destabilizing	0.991	D	0.503	neutral	None	None	None	None	N
S/Q	0.3885	ambiguous	0.2729	benign	-0.391	Destabilizing	0.949	D	0.453	neutral	None	None	None	None	N
S/R	0.5013	ambiguous	0.3248	benign	-0.163	Destabilizing	0.801	D	0.491	neutral	N	0.431715461	None	None	N
S/T	0.0884	likely_benign	0.0871	benign	-0.239	Destabilizing	0.801	D	0.409	neutral	N	0.431542103	None	None	N
S/V	0.1698	likely_benign	0.1647	benign	-0.1	Destabilizing	0.974	D	0.538	neutral	None	None	None	None	N
S/W	0.351	ambiguous	0.3041	benign	-0.934	Destabilizing	0.998	D	0.611	neutral	None	None	None	None	N
S/Y	0.1636	likely_benign	0.1479	benign	-0.624	Destabilizing	0.949	D	0.546	neutral	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.