TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21447	64564;64565;64566	chr2:178586562;178586561;178586560	chr2:179451289;179451288;179451287
N2AB	19806	59641;59642;59643	chr2:178586562;178586561;178586560	chr2:179451289;179451288;179451287
N2A	18879	56860;56861;56862	chr2:178586562;178586561;178586560	chr2:179451289;179451288;179451287
N2B	12382	37369;37370;37371	chr2:178586562;178586561;178586560	chr2:179451289;179451288;179451287
Novex-1	12507	37744;37745;37746	chr2:178586562;178586561;178586560	chr2:179451289;179451288;179451287
Novex-2	12574	37945;37946;37947	chr2:178586562;178586561;178586560	chr2:179451289;179451288;179451287
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-43
• Domain position: 82
• Structural Position: 114
• Q(SASA): 0.5569
• 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
V/A	rs2049030119	None	0.992	N	0.482	0.339	0.480574121323	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/A	rs2049030119	None	0.992	N	0.482	0.339	0.480574121323	gnomAD-4.0.0	3.09964E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.23943E-06	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
V/A	0.1644	likely_benign	0.127	benign	-0.287	Destabilizing	0.992	D	0.482	neutral	N	0.408388389	None	None	I
V/C	0.7668	likely_pathogenic	0.7082	pathogenic	-0.629	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	I
V/D	0.8529	likely_pathogenic	0.7251	pathogenic	-0.282	Destabilizing	1.0	D	0.819	deleterious	N	0.503434778	None	None	I
V/E	0.7047	likely_pathogenic	0.5753	pathogenic	-0.414	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
V/F	0.2965	likely_benign	0.2123	benign	-0.646	Destabilizing	0.999	D	0.751	deleterious	N	0.487486678	None	None	I
V/G	0.4259	ambiguous	0.322	benign	-0.372	Destabilizing	1.0	D	0.791	deleterious	N	0.483982226	None	None	I
V/H	0.7962	likely_pathogenic	0.677	pathogenic	0.059	Stabilizing	1.0	D	0.822	deleterious	None	None	None	None	I
V/I	0.1025	likely_benign	0.092	benign	-0.222	Destabilizing	0.619	D	0.327	neutral	N	0.417760021	None	None	I
V/K	0.7017	likely_pathogenic	0.5482	ambiguous	-0.261	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
V/L	0.3979	ambiguous	0.2787	benign	-0.222	Destabilizing	0.962	D	0.521	neutral	N	0.472421225	None	None	I
V/M	0.2454	likely_benign	0.1947	benign	-0.315	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	I
V/N	0.6081	likely_pathogenic	0.4546	ambiguous	-0.037	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
V/P	0.8951	likely_pathogenic	0.8675	pathogenic	-0.211	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
V/Q	0.5865	likely_pathogenic	0.4588	ambiguous	-0.31	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
V/R	0.5893	likely_pathogenic	0.4302	ambiguous	0.264	Stabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
V/S	0.3318	likely_benign	0.2354	benign	-0.361	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	I
V/T	0.2551	likely_benign	0.1856	benign	-0.397	Destabilizing	0.997	D	0.71	prob.delet.	None	None	None	None	I
V/W	0.9208	likely_pathogenic	0.8575	pathogenic	-0.701	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	I
V/Y	0.7736	likely_pathogenic	0.6381	pathogenic	-0.393	Destabilizing	1.0	D	0.759	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.