TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29810	89653;89654;89655	chr2:178553577;178553576;178553575	chr2:179418304;179418303;179418302
N2AB	28169	84730;84731;84732	chr2:178553577;178553576;178553575	chr2:179418304;179418303;179418302
N2A	27242	81949;81950;81951	chr2:178553577;178553576;178553575	chr2:179418304;179418303;179418302
N2B	20745	62458;62459;62460	chr2:178553577;178553576;178553575	chr2:179418304;179418303;179418302
Novex-1	20870	62833;62834;62835	chr2:178553577;178553576;178553575	chr2:179418304;179418303;179418302
Novex-2	20937	63034;63035;63036	chr2:178553577;178553576;178553575	chr2:179418304;179418303;179418302
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-105
• Domain position: 77
• Structural Position: 108
• Q(SASA): 0.0848
• 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
V/I	rs745716789	-0.864	0.997	D	0.65	0.377	0.746583782714	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
V/I	rs745716789	-0.864	0.997	D	0.65	0.377	0.746583782714	gnomAD-4.0.0	1.59117E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43283E-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
V/A	0.868	likely_pathogenic	0.837	pathogenic	-2.666	Highly Destabilizing	0.999	D	0.68	prob.neutral	D	0.53371685	None	None	N
V/C	0.9562	likely_pathogenic	0.9553	pathogenic	-2.097	Highly Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
V/D	0.9977	likely_pathogenic	0.9976	pathogenic	-3.622	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
V/E	0.9936	likely_pathogenic	0.9937	pathogenic	-3.318	Highly Destabilizing	1.0	D	0.888	deleterious	D	0.629947995	None	None	N
V/F	0.8798	likely_pathogenic	0.8568	pathogenic	-1.528	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/G	0.932	likely_pathogenic	0.9194	pathogenic	-3.238	Highly Destabilizing	1.0	D	0.891	deleterious	D	0.629947995	None	None	N
V/H	0.998	likely_pathogenic	0.9978	pathogenic	-3.014	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/I	0.0992	likely_benign	0.0957	benign	-0.987	Destabilizing	0.997	D	0.65	neutral	D	0.537700147	None	None	N
V/K	0.9944	likely_pathogenic	0.9944	pathogenic	-2.267	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
V/L	0.7081	likely_pathogenic	0.6924	pathogenic	-0.987	Destabilizing	0.997	D	0.697	prob.neutral	N	0.505467149	None	None	N
V/M	0.7709	likely_pathogenic	0.753	pathogenic	-1.226	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
V/N	0.9923	likely_pathogenic	0.9912	pathogenic	-2.914	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
V/P	0.995	likely_pathogenic	0.994	pathogenic	-1.532	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
V/Q	0.9925	likely_pathogenic	0.992	pathogenic	-2.595	Highly Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
V/R	0.9896	likely_pathogenic	0.9895	pathogenic	-2.218	Highly Destabilizing	1.0	D	0.904	deleterious	None	None	None	None	N
V/S	0.9718	likely_pathogenic	0.9655	pathogenic	-3.409	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
V/T	0.9258	likely_pathogenic	0.9187	pathogenic	-2.963	Highly Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
V/W	0.9983	likely_pathogenic	0.9981	pathogenic	-2.096	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/Y	0.9876	likely_pathogenic	0.9862	pathogenic	-1.843	Destabilizing	1.0	D	0.84	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.