TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8697	26314;26315;26316	chr2:178715097;178715096;178715095	chr2:179579824;179579823;179579822
N2AB	8380	25363;25364;25365	chr2:178715097;178715096;178715095	chr2:179579824;179579823;179579822
N2A	7453	22582;22583;22584	chr2:178715097;178715096;178715095	chr2:179579824;179579823;179579822
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: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-72
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.2491
• 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/R	rs1364653469	-0.44	0.141	N	0.617	0.203	0.659087871485	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
L/R	rs1364653469	-0.44	0.141	N	0.617	0.203	0.659087871485	gnomAD-4.0.0	3.18283E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86574E-05	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	0.2003	likely_benign	0.1769	benign	-1.562	Destabilizing	0.031	N	0.477	neutral	None	None	None	None	N
L/C	0.3778	ambiguous	0.3497	ambiguous	-0.889	Destabilizing	0.807	D	0.551	neutral	None	None	None	None	N
L/D	0.5138	ambiguous	0.4381	ambiguous	-1.328	Destabilizing	0.135	N	0.639	neutral	None	None	None	None	N
L/E	0.2517	likely_benign	0.2185	benign	-1.372	Destabilizing	0.103	N	0.622	neutral	None	None	None	None	N
L/F	0.0977	likely_benign	0.0873	benign	-1.354	Destabilizing	0.178	N	0.521	neutral	None	None	None	None	N
L/G	0.4631	ambiguous	0.3939	ambiguous	-1.835	Destabilizing	0.135	N	0.613	neutral	None	None	None	None	N
L/H	0.1094	likely_benign	0.099	benign	-1.134	Destabilizing	None	N	0.484	neutral	None	None	None	None	N
L/I	0.08	likely_benign	0.0758	benign	-0.902	Destabilizing	None	N	0.213	neutral	N	0.492575572	None	None	N
L/K	0.1701	likely_benign	0.1544	benign	-0.925	Destabilizing	0.005	N	0.601	neutral	None	None	None	None	N
L/M	0.1092	likely_benign	0.1064	benign	-0.587	Destabilizing	0.061	N	0.527	neutral	None	None	None	None	N
L/N	0.2438	likely_benign	0.2158	benign	-0.675	Destabilizing	0.135	N	0.641	neutral	None	None	None	None	N
L/P	0.7643	likely_pathogenic	0.634	pathogenic	-1.091	Destabilizing	0.455	N	0.634	neutral	N	0.497644973	None	None	N
L/Q	0.0872	likely_benign	0.0818	benign	-0.964	Destabilizing	0.146	N	0.606	neutral	N	0.509699895	None	None	N
L/R	0.1112	likely_benign	0.1	benign	-0.3	Destabilizing	0.141	N	0.617	neutral	N	0.492575572	None	None	N
L/S	0.1695	likely_benign	0.146	benign	-1.206	Destabilizing	0.003	N	0.341	neutral	None	None	None	None	N
L/T	0.1533	likely_benign	0.1387	benign	-1.146	Destabilizing	0.001	N	0.255	neutral	None	None	None	None	N
L/V	0.0823	likely_benign	0.0767	benign	-1.091	Destabilizing	None	N	0.156	neutral	N	0.490383415	None	None	N
L/W	0.1787	likely_benign	0.146	benign	-1.389	Destabilizing	0.95	D	0.616	neutral	None	None	None	None	N
L/Y	0.2324	likely_benign	0.1984	benign	-1.15	Destabilizing	0.013	N	0.591	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.