TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2083	6472;6473;6474	chr2:178775617;178775616;178775615	chr2:179640344;179640343;179640342
N2AB	2083	6472;6473;6474	chr2:178775617;178775616;178775615	chr2:179640344;179640343;179640342
N2A	2083	6472;6473;6474	chr2:178775617;178775616;178775615	chr2:179640344;179640343;179640342
N2B	2037	6334;6335;6336	chr2:178775617;178775616;178775615	chr2:179640344;179640343;179640342
Novex-1	2037	6334;6335;6336	chr2:178775617;178775616;178775615	chr2:179640344;179640343;179640342
Novex-2	2037	6334;6335;6336	chr2:178775617;178775616;178775615	chr2:179640344;179640343;179640342
Novex-3	2083	6472;6473;6474	chr2:178775617;178775616;178775615	chr2:179640344;179640343;179640342

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-10
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.5613
• Predicted PPI site: I

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
R/G	None	None	0.645	N	0.647	0.33	0.529411561632	gnomAD-4.0.0	1.59059E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85654E-06	0	0
R/I	rs781676050	0.613	0.928	N	0.769	0.38	0.649559452448	gnomAD-4.0.0	9.54356E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.71393E-05	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
R/A	0.9436	likely_pathogenic	0.948	pathogenic	-0.292	Destabilizing	0.547	D	0.619	neutral	None	None	None	None	I
R/C	0.8674	likely_pathogenic	0.9128	pathogenic	-0.483	Destabilizing	0.995	D	0.74	deleterious	None	None	None	None	I
R/D	0.9758	likely_pathogenic	0.978	pathogenic	0.013	Stabilizing	0.894	D	0.725	prob.delet.	None	None	None	None	I
R/E	0.9108	likely_pathogenic	0.9177	pathogenic	0.111	Stabilizing	0.547	D	0.559	neutral	None	None	None	None	I
R/F	0.9801	likely_pathogenic	0.9792	pathogenic	-0.338	Destabilizing	0.981	D	0.75	deleterious	None	None	None	None	I
R/G	0.857	likely_pathogenic	0.8681	pathogenic	-0.539	Destabilizing	0.645	D	0.647	neutral	N	0.455536882	None	None	I
R/H	0.5342	ambiguous	0.5863	pathogenic	-0.886	Destabilizing	0.945	D	0.673	neutral	None	None	None	None	I
R/I	0.9471	likely_pathogenic	0.9435	pathogenic	0.342	Stabilizing	0.928	D	0.769	deleterious	N	0.506686501	None	None	I
R/K	0.2812	likely_benign	0.2724	benign	-0.348	Destabilizing	0.006	N	0.251	neutral	N	0.469555164	None	None	I
R/L	0.8812	likely_pathogenic	0.8876	pathogenic	0.342	Stabilizing	0.707	D	0.647	neutral	None	None	None	None	I
R/M	0.9246	likely_pathogenic	0.9221	pathogenic	-0.149	Destabilizing	0.995	D	0.725	prob.delet.	None	None	None	None	I
R/N	0.9625	likely_pathogenic	0.9665	pathogenic	-0.113	Destabilizing	0.894	D	0.642	neutral	None	None	None	None	I
R/P	0.9074	likely_pathogenic	0.9207	pathogenic	0.152	Stabilizing	0.945	D	0.756	deleterious	None	None	None	None	I
R/Q	0.5087	ambiguous	0.5788	pathogenic	-0.203	Destabilizing	0.809	D	0.637	neutral	None	None	None	None	I
R/S	0.9663	likely_pathogenic	0.9723	pathogenic	-0.636	Destabilizing	0.477	N	0.689	prob.neutral	N	0.507326666	None	None	I
R/T	0.9294	likely_pathogenic	0.935	pathogenic	-0.378	Destabilizing	0.864	D	0.721	prob.delet.	N	0.498678418	None	None	I
R/V	0.9473	likely_pathogenic	0.9472	pathogenic	0.152	Stabilizing	0.894	D	0.753	deleterious	None	None	None	None	I
R/W	0.8564	likely_pathogenic	0.868	pathogenic	-0.233	Destabilizing	0.995	D	0.719	prob.delet.	None	None	None	None	I
R/Y	0.9464	likely_pathogenic	0.9476	pathogenic	0.131	Stabilizing	0.981	D	0.754	deleterious	None	None	None	None	I

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.