TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20344	61255;61256;61257	chr2:178590695;178590694;178590693	chr2:179455422;179455421;179455420
N2AB	18703	56332;56333;56334	chr2:178590695;178590694;178590693	chr2:179455422;179455421;179455420
N2A	17776	53551;53552;53553	chr2:178590695;178590694;178590693	chr2:179455422;179455421;179455420
N2B	11279	34060;34061;34062	chr2:178590695;178590694;178590693	chr2:179455422;179455421;179455420
Novex-1	11404	34435;34436;34437	chr2:178590695;178590694;178590693	chr2:179455422;179455421;179455420
Novex-2	11471	34636;34637;34638	chr2:178590695;178590694;178590693	chr2:179455422;179455421;179455420
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-35
• Domain position: 74
• Structural Position: 107
• Q(SASA): 0.1416
• 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
R/I	None	None	1.0	N	0.834	0.482	0.651161722719	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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
R/A	0.9716	likely_pathogenic	0.9797	pathogenic	-2.238	Highly Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
R/C	0.4514	ambiguous	0.5732	pathogenic	-1.947	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
R/D	0.9974	likely_pathogenic	0.9983	pathogenic	-1.093	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
R/E	0.9559	likely_pathogenic	0.9658	pathogenic	-0.862	Destabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	N
R/F	0.9771	likely_pathogenic	0.9906	pathogenic	-1.4	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
R/G	0.9732	likely_pathogenic	0.9809	pathogenic	-2.578	Highly Destabilizing	1.0	D	0.747	deleterious	D	0.556452919	None	None	N
R/H	0.2328	likely_benign	0.469	ambiguous	-2.196	Highly Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
R/I	0.9368	likely_pathogenic	0.9483	pathogenic	-1.233	Destabilizing	1.0	D	0.834	deleterious	N	0.513002707	None	None	N
R/K	0.3818	ambiguous	0.4752	ambiguous	-1.151	Destabilizing	0.997	D	0.675	prob.neutral	N	0.49819968	None	None	N
R/L	0.8708	likely_pathogenic	0.9038	pathogenic	-1.233	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
R/M	0.9208	likely_pathogenic	0.9486	pathogenic	-1.707	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
R/N	0.9838	likely_pathogenic	0.992	pathogenic	-1.33	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
R/P	0.9991	likely_pathogenic	0.9991	pathogenic	-1.561	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
R/Q	0.3312	likely_benign	0.3931	ambiguous	-1.201	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
R/S	0.9774	likely_pathogenic	0.9859	pathogenic	-2.27	Highly Destabilizing	1.0	D	0.752	deleterious	N	0.515138619	None	None	N
R/T	0.9577	likely_pathogenic	0.9724	pathogenic	-1.822	Destabilizing	1.0	D	0.752	deleterious	N	0.502896941	None	None	N
R/V	0.9414	likely_pathogenic	0.9558	pathogenic	-1.561	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
R/W	0.7249	likely_pathogenic	0.8341	pathogenic	-0.852	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
R/Y	0.9195	likely_pathogenic	0.968	pathogenic	-0.778	Destabilizing	1.0	D	0.83	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.